Hispana. Acceso en línea al Patrimonio Cultural Digital Español

Está en:  › Erregistro

α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice

Identificadores del recurso

Pharmaceutics 13(6) : (2021) // Article ID 771

1999-4923

http://hdl.handle.net/10810/52184

10.3390/pharmaceutics13060771

Jatorria

(ADDI)

Fitxa

Izenburu:: α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice
Tema:: gene therapy; non-viral vectors; solid lipid nanoparticles; pDNA; Fabry disease; Fabry mice; α-galactosidase A; intravenous administration
Deskribapen:: Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.; This research was funded by Merck Salud Foundation, MCIU/AEI/FEDER, UE (RTI2018-098672-B-I00) and by the University of the Basque Country UPV/EHU (GIU17/032).
Idioma:: English
Harreman:: info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00; https://www.mdpi.com/1999-4923/13/6/771
Autor/Productor:: Rodríguez Castejón, Julen; Alarcia Lacalle, Ana; Gómez Aguado, Itziar; Vicente Pascual, Mónica; Solinís Aspiazu, María Ángeles; Del Pozo Rodríguez, Ana; Rodríguez Gascón, Alicia
Argitaratzaile:: MDPI
Eskubideak:: info:eu-repo/semantics/openAccess; http://creativecommons.org/licenses/by/3.0/es/; © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Data:: 2021-07-08T16:39:17Z; 2021-05-21; 2021-06-24T14:11:30Z
Tipo de recurso:: info:eu-repo/semantics/article
Formatu:: application/pdf

oai_dc

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<oai_dc:dc schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
1. <dc:title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</dc:title>
2. <dc:creator>Rodríguez Castejón, Julen</dc:creator>
3. <dc:creator>Alarcia Lacalle, Ana</dc:creator>
4. <dc:creator>Gómez Aguado, Itziar</dc:creator>
5. <dc:creator>Vicente Pascual, Mónica</dc:creator>
6. <dc:creator>Solinís Aspiazu, María Ángeles</dc:creator>
7. <dc:creator>Del Pozo Rodríguez, Ana</dc:creator>
8. <dc:creator>Rodríguez Gascón, Alicia</dc:creator>
9. <dc:subject>gene therapy</dc:subject>
10. <dc:subject>non-viral vectors</dc:subject>
11. <dc:subject>solid lipid nanoparticles</dc:subject>
12. <dc:subject>pDNA</dc:subject>
13. <dc:subject>Fabry disease</dc:subject>
14. <dc:subject>Fabry mice</dc:subject>
15. <dc:subject>α-galactosidase A</dc:subject>
16. <dc:subject>intravenous administration</dc:subject>
17. <dc:description>Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</dc:description>
18. <dc:description>This research was funded by Merck Salud Foundation, MCIU/AEI/FEDER, UE (RTI2018-098672-B-I00) and by the University of the Basque Country UPV/EHU (GIU17/032).</dc:description>
19. <dc:date>2021-07-08T16:39:17Z</dc:date>
20. <dc:date>2021-07-08T16:39:17Z</dc:date>
21. <dc:date>2021-05-21</dc:date>
22. <dc:date>2021-06-24T14:11:30Z</dc:date>
23. <dc:type>info:eu-repo/semantics/article</dc:type>
24. <dc:identifier>Pharmaceutics 13(6) : (2021) // Article ID 771</dc:identifier>
25. <dc:identifier>1999-4923</dc:identifier>
26. <dc:identifier>http://hdl.handle.net/10810/52184</dc:identifier>
27. <dc:identifier>10.3390/pharmaceutics13060771</dc:identifier>
28. <dc:language>eng</dc:language>
29. <dc:relation>info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</dc:relation>
30. <dc:relation>https://www.mdpi.com/1999-4923/13/6/771</dc:relation>
31. <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
32. <dc:rights>http://creativecommons.org/licenses/by/3.0/es/</dc:rights>
33. <dc:rights>© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</dc:rights>
34. <dc:format>application/pdf</dc:format>
35. <dc:publisher>MDPI</dc:publisher>
</oai_dc:dc>

didl

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<d:DIDL schemaLocation="urn:mpeg:mpeg21:2002:02-DIDL-NS http://standards.iso.org/ittf/PubliclyAvailableStandards/MPEG-21_schema_files/did/didl.xsd">
1. <d:DIDLInfo>
  1. <dcterms:created schemaLocation="http://purl.org/dc/terms/ http://dublincore.org/schemas/xmls/qdc/dcterms.xsd">2021-07-08T16:39:17Z</dcterms:created>
  </d:DIDLInfo>
2. <d:Item id="hdl_10810_52184">
  1. <d:Descriptor>
    1. <d:Statement mimeType="application/xml; charset=utf-8">
      1. <dii:Identifier schemaLocation="urn:mpeg:mpeg21:2002:01-DII-NS http://standards.iso.org/ittf/PubliclyAvailableStandards/MPEG-21_schema_files/dii/dii.xsd">urn:hdl:10810/52184</dii:Identifier>
      </d:Statement>
    </d:Descriptor>
  2. <d:Descriptor>
    1. <d:Statement mimeType="application/xml; charset=utf-8">
      1. <oai_dc:dc schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
        <dc:title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</dc:title>
        <dc:creator>Rodríguez Castejón, Julen</dc:creator>
        <dc:creator>Alarcia Lacalle, Ana</dc:creator>
        <dc:creator>Gómez Aguado, Itziar</dc:creator>
        <dc:creator>Vicente Pascual, Mónica</dc:creator>
        <dc:creator>Solinís Aspiazu, María Ángeles</dc:creator>
        <dc:creator>Del Pozo Rodríguez, Ana</dc:creator>
        <dc:creator>Rodríguez Gascón, Alicia</dc:creator>
        <dc:subject>gene therapy</dc:subject>
        <dc:subject>non-viral vectors</dc:subject>
        <dc:subject>solid lipid nanoparticles</dc:subject>
        <dc:subject>pDNA</dc:subject>
        <dc:subject>Fabry disease</dc:subject>
        <dc:subject>Fabry mice</dc:subject>
        <dc:subject>α-galactosidase A</dc:subject>
        <dc:subject>intravenous administration</dc:subject>
        <dc:description>Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</dc:description>
        <dc:date>2021-07-08T16:39:17Z</dc:date>
        <dc:date>2021-07-08T16:39:17Z</dc:date>
        <dc:date>2021-05-21</dc:date>
        <dc:date>2021-06-24T14:11:30Z</dc:date>
        <dc:type>info:eu-repo/semantics/article</dc:type>
        <dc:identifier>Pharmaceutics 13(6) : (2021) // Article ID 771</dc:identifier>
        <dc:identifier>1999-4923</dc:identifier>
        <dc:identifier>http://hdl.handle.net/10810/52184</dc:identifier>
        <dc:identifier>10.3390/pharmaceutics13060771</dc:identifier>
        <dc:language>eng</dc:language>
        <dc:relation>https://www.mdpi.com/1999-4923/13/6/771</dc:relation>
        <dc:relation>info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</dc:relation>
        <dc:rights>http://creativecommons.org/licenses/by/3.0/es/</dc:rights>
        <dc:rights>© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</dc:rights>
        <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
        <dc:publisher>MDPI</dc:publisher>
        </oai_dc:dc>
      </d:Statement>
    </d:Descriptor>
  3. <d:Component id="10810_52184_1">
    1. <d:Resource mimeType="application/pdf" ref="http://addi.ehu.es/bitstream/10810/52184/1/pharmaceutics-13-00771-v2.pdf" />
    </d:Component>
  </d:Item>
</d:DIDL>

dim

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<dim:dim schemaLocation="http://www.dspace.org/xmlns/dspace/dim http://www.dspace.org/schema/dim.xsd">
1. <dim:field authority="14cefb36-55d4-470d-b67e-16171ca4e8ec" confidence="600" element="contributor" mdschema="dc" qualifier="author">Rodríguez Castejón, Julen</dim:field>
2. <dim:field element="contributor" mdschema="dc" qualifier="author">Alarcia Lacalle, Ana</dim:field>
3. <dim:field authority="bc069c0f-cc81-48db-8821-6c63754084c5" confidence="600" element="contributor" mdschema="dc" qualifier="author">Gómez Aguado, Itziar</dim:field>
4. <dim:field element="contributor" mdschema="dc" qualifier="author">Vicente Pascual, Mónica</dim:field>
5. <dim:field authority="91649621-546b-4ecd-a219-4cc1b801a451" confidence="600" element="contributor" mdschema="dc" qualifier="author">Solinís Aspiazu, María Ángeles</dim:field>
6. <dim:field authority="06123ee8-8fcd-4596-a206-27c2dfa8af04" confidence="600" element="contributor" mdschema="dc" qualifier="author">Del Pozo Rodríguez, Ana</dim:field>
7. <dim:field authority="3467a71f-4ba6-4b7b-8a7b-d391a93df83e" confidence="600" element="contributor" mdschema="dc" qualifier="author">Rodríguez Gascón, Alicia</dim:field>
8. <dim:field element="date" mdschema="dc" qualifier="accessioned">2021-07-08T16:39:17Z</dim:field>
9. <dim:field element="date" mdschema="dc" qualifier="available">2021-07-08T16:39:17Z</dim:field>
10. <dim:field element="date" mdschema="dc" qualifier="issued">2021-05-21</dim:field>
11. <dim:field element="date" mdschema="dc" qualifier="updated">2021-06-24T14:11:30Z</dim:field>
12. <dim:field element="identifier" lang="es_ES" mdschema="dc" qualifier="citation">Pharmaceutics 13(6) : (2021) // Article ID 771</dim:field>
13. <dim:field element="identifier" mdschema="dc" qualifier="issn">1999-4923</dim:field>
14. <dim:field element="identifier" mdschema="dc" qualifier="uri">http://hdl.handle.net/10810/52184</dim:field>
15. <dim:field element="identifier" mdschema="dc" qualifier="doi">10.3390/pharmaceutics13060771</dim:field>
16. <dim:field element="description" lang="es_ES" mdschema="dc" qualifier="abstract">Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</dim:field>
17. <dim:field element="description" lang="es_ES" mdschema="dc" qualifier="sponsorship">This research was funded by Merck Salud Foundation, MCIU/AEI/FEDER, UE (RTI2018-098672-B-I00) and by the University of the Basque Country UPV/EHU (GIU17/032).</dim:field>
18. <dim:field element="language" lang="es_ES" mdschema="dc" qualifier="iso">eng</dim:field>
19. <dim:field element="publisher" lang="es_ES" mdschema="dc">MDPI</dim:field>
20. <dim:field element="relation" lang="es_ES" mdschema="dc">info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</dim:field>
21. <dim:field element="relation" lang="es_ES" mdschema="dc" qualifier="publisherversion">https://www.mdpi.com/1999-4923/13/6/771</dim:field>
22. <dim:field element="rights" lang="es_ES" mdschema="dc">info:eu-repo/semantics/openAccess</dim:field>
23. <dim:field element="rights" mdschema="dc" qualifier="uri">http://creativecommons.org/licenses/by/3.0/es/</dim:field>
24. <dim:field element="rights" lang="es_ES" mdschema="dc" qualifier="holder">© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</dim:field>
25. <dim:field element="subject" lang="es_ES" mdschema="dc">gene therapy</dim:field>
26. <dim:field element="subject" lang="es_ES" mdschema="dc">non-viral vectors</dim:field>
27. <dim:field element="subject" lang="es_ES" mdschema="dc">solid lipid nanoparticles</dim:field>
28. <dim:field element="subject" lang="es_ES" mdschema="dc">pDNA</dim:field>
29. <dim:field element="subject" lang="es_ES" mdschema="dc">Fabry disease</dim:field>
30. <dim:field element="subject" lang="es_ES" mdschema="dc">Fabry mice</dim:field>
31. <dim:field element="subject" lang="es_ES" mdschema="dc">α-galactosidase A</dim:field>
32. <dim:field element="subject" lang="es_ES" mdschema="dc">intravenous administration</dim:field>
33. <dim:field element="title" lang="es_ES" mdschema="dc">α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</dim:field>
34. <dim:field element="type" lang="es_ES" mdschema="dc">info:eu-repo/semantics/article</dim:field>
35. <dim:field element="departamentoes" mdschema="dc">Farmacia y ciencias de los alimentos</dim:field>
36. <dim:field element="departamentoeu" mdschema="dc">Farmazia eta elikagaien zientziak</dim:field>
</dim:dim>

edm

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<rdf:RDF schemaLocation="http://www.w3.org/1999/02/22-rdf-syntax-ns# http://www.europeana.eu/schemas/edm/EDM.xsd">
1. <edm:ProvidedCHO about="http://hdl.handle.net/10810/52184">
  1. <dc:contributor>This research was funded by Merck Salud Foundation, MCIU/AEI/FEDER, UE (RTI2018-098672-B-I00) and by the University of the Basque Country UPV/EHU (GIU17/032).</dc:contributor>
  2. <dc:creator>Rodríguez Castejón, Julen</dc:creator>
  3. <dc:creator>Alarcia Lacalle, Ana</dc:creator>
  4. <dc:creator>Gómez Aguado, Itziar</dc:creator>
  5. <dc:creator>Vicente Pascual, Mónica</dc:creator>
  6. <dc:creator>Solinís Aspiazu, María Ángeles</dc:creator>
  7. <dc:creator>Del Pozo Rodríguez, Ana</dc:creator>
  8. <dc:creator>Rodríguez Gascón, Alicia</dc:creator>
  9. <dc:description lang="es-ES">Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</dc:description>
  10. <dc:identifier>Pharmaceutics 13(6) : (2021) // Article ID 771</dc:identifier>
  11. <dc:identifier>http://hdl.handle.net/10810/52184</dc:identifier>
  12. <dc:identifier>10.3390/pharmaceutics13060771</dc:identifier>
  13. <dc:language>eng</dc:language>
  14. <dc:publisher>MDPI</dc:publisher>
  15. <dc:relation>1999-4923</dc:relation>
  16. <dc:relation>http://hdl.handle.net/10810/52184</dc:relation>
  17. <dc:relation>info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</dc:relation>
  18. <dc:subject resource="10810/52184:gene therapy" lang="es-ES" />
  19. <dc:subject resource="10810/52184:non-viral vectors" lang="es-ES" />
  20. <dc:subject resource="10810/52184:solid lipid nanoparticles" lang="es-ES" />
  21. <dc:subject resource="10810/52184:pDNA" lang="es-ES" />
  22. <dc:subject resource="10810/52184:Fabry disease" lang="es-ES" />
  23. <dc:subject resource="10810/52184:Fabry mice" lang="es-ES" />
  24. <dc:subject resource="10810/52184:α-galactosidase A" lang="es-ES" />
  25. <dc:subject resource="10810/52184:intravenous administration" lang="es-ES" />
  26. <dcterms:issued>2021-05-21</dcterms:issued>
  27. <dcterms:isFormatOf>https://www.mdpi.com/1999-4923/13/6/771</dcterms:isFormatOf>
  28. <dc:title lang="es-ES">α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</dc:title>
  29. <dc:type>info:eu-repo/semantics/article</dc:type>
  30. <edm:type>TEXT</edm:type>
  </edm:ProvidedCHO>
2. <skos:Concept about="10810/52184:gene therapy">
  1. <skos:prefLabel lang="es-ES">gene therapy</skos:prefLabel>
  2. <skos:inScheme resource="http://vocabularies.unesco.org/browser/thesaurus/es/search/?q=gene therapy" />
  </skos:Concept>
3. <skos:Concept about="10810/52184:non-viral vectors">
  1. <skos:prefLabel lang="es-ES">non-viral vectors</skos:prefLabel>
  2. <skos:inScheme resource="http://vocabularies.unesco.org/browser/thesaurus/es/search/?q=non-viral vectors" />
  </skos:Concept>
4. <skos:Concept about="10810/52184:solid lipid nanoparticles">
  1. <skos:prefLabel lang="es-ES">solid lipid nanoparticles</skos:prefLabel>
  2. <skos:inScheme resource="http://vocabularies.unesco.org/browser/thesaurus/es/search/?q=solid lipid nanoparticles" />
  </skos:Concept>
5. <skos:Concept about="10810/52184:pDNA">
  1. <skos:prefLabel lang="es-ES">pDNA</skos:prefLabel>
  2. <skos:inScheme resource="http://vocabularies.unesco.org/browser/thesaurus/es/search/?q=pDNA" />
  </skos:Concept>
6. <skos:Concept about="10810/52184:Fabry disease">
  1. <skos:prefLabel lang="es-ES">Fabry disease</skos:prefLabel>
  2. <skos:inScheme resource="http://vocabularies.unesco.org/browser/thesaurus/es/search/?q=Fabry disease" />
  </skos:Concept>
7. <skos:Concept about="10810/52184:Fabry mice">
  1. <skos:prefLabel lang="es-ES">Fabry mice</skos:prefLabel>
  2. <skos:inScheme resource="http://vocabularies.unesco.org/browser/thesaurus/es/search/?q=Fabry mice" />
  </skos:Concept>
8. <skos:Concept about="10810/52184:α-galactosidase A">
  1. <skos:prefLabel lang="es-ES">α-galactosidase A</skos:prefLabel>
  2. <skos:inScheme resource="http://vocabularies.unesco.org/browser/thesaurus/es/search/?q=α-galactosidase A" />
  </skos:Concept>
9. <skos:Concept about="10810/52184:intravenous administration">
  1. <skos:prefLabel lang="es-ES">intravenous administration</skos:prefLabel>
  2. <skos:inScheme resource="http://vocabularies.unesco.org/browser/thesaurus/es/search/?q=intravenous administration" />
  </skos:Concept>
10. <ore:Aggregation about="http://hdl.handle.net/10810/52184#aggregation ">
  1. <edm:aggregatedCHO resource="http://hdl.handle.net/10810/52184" />
  2. <edm:dataProvider>Biblioteca de la Universidad del Pais Vasco/Euskal Herriko Unibertsitatea Biblioteka</edm:dataProvider>
  3. <edm:isShownAt resource="http://hdl.handle.net/10810/52184" />
  4. <edm:isShownBy resource="http://addi.ehu.es/bitstream/10810/52184/1/pharmaceutics-13-00771-v2.pdf" />
  5. <edm:hasView resource="http://addi.ehu.es/bitstream/10810/52184/1/pharmaceutics-13-00771-v2.pdf" />
  6. <edm:object />
  7. <edm:provider>Hispana</edm:provider>
  8. <edm:intermediateProvider>ADDI (Universidad del Pais Vasco/Euskal Herriko Unibertsitatea, Spain)</edm:intermediateProvider>
  9. <edm:rights resource="http://creativecommons.org/licenses/by/4.0/" />
  </ore:Aggregation>
11. <edm:WebResource about="http://hdl.handle.net/10810/52184">
  1. <edm:rights resource="http://creativecommons.org/licenses/by/4.0/" />
  </edm:WebResource>
</rdf:RDF>

etdms

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<thesis schemaLocation="http://www.ndltd.org/standards/metadata/etdms/1.0/ http://www.ndltd.org/standards/metadata/etdms/1.0/etdms.xsd">
1. <title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</title>
2. <creator>Rodríguez Castejón, Julen</creator>
3. <creator>Alarcia Lacalle, Ana</creator>
4. <creator>Gómez Aguado, Itziar</creator>
5. <creator>Vicente Pascual, Mónica</creator>
6. <creator>Solinís Aspiazu, María Ángeles</creator>
7. <creator>Del Pozo Rodríguez, Ana</creator>
8. <creator>Rodríguez Gascón, Alicia</creator>
9. <subject>gene therapy</subject>
10. <subject>non-viral vectors</subject>
11. <subject>solid lipid nanoparticles</subject>
12. <subject>pDNA</subject>
13. <subject>Fabry disease</subject>
14. <subject>Fabry mice</subject>
15. <subject>α-galactosidase A</subject>
16. <subject>intravenous administration</subject>
17. <description>Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</description>
18. <date>2021-07-08</date>
19. <date>2021-07-08</date>
20. <date>2021-05-21</date>
21. <date>2021-06-24</date>
22. <type>info:eu-repo/semantics/article</type>
23. <identifier>Pharmaceutics 13(6) : (2021) // Article ID 771</identifier>
24. <identifier>1999-4923</identifier>
25. <identifier>http://hdl.handle.net/10810/52184</identifier>
26. <identifier>10.3390/pharmaceutics13060771</identifier>
27. <language>eng</language>
28. <relation>https://www.mdpi.com/1999-4923/13/6/771</relation>
29. <relation>info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</relation>
30. <rights>http://creativecommons.org/licenses/by/3.0/es/</rights>
31. <rights>© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</rights>
32. <rights>info:eu-repo/semantics/openAccess</rights>
33. <publisher>MDPI</publisher>
</thesis>

marc

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<record schemaLocation="http://www.loc.gov/MARC21/slim http://www.loc.gov/standards/marcxml/schema/MARC21slim.xsd">
1. <leader>00925njm 22002777a 4500</leader>
2. <datafield ind1=" " ind2=" " tag="042">
  1. <subfield code="a">dc</subfield>
  </datafield>
3. <datafield ind1=" " ind2=" " tag="720">
  1. <subfield code="a">Rodríguez Castejón, Julen</subfield>
  2. <subfield code="e">author</subfield>
  </datafield>
4. <datafield ind1=" " ind2=" " tag="720">
  1. <subfield code="a">Alarcia Lacalle, Ana</subfield>
  2. <subfield code="e">author</subfield>
  </datafield>
5. <datafield ind1=" " ind2=" " tag="720">
  1. <subfield code="a">Gómez Aguado, Itziar</subfield>
  2. <subfield code="e">author</subfield>
  </datafield>
6. <datafield ind1=" " ind2=" " tag="720">
  1. <subfield code="a">Vicente Pascual, Mónica</subfield>
  2. <subfield code="e">author</subfield>
  </datafield>
7. <datafield ind1=" " ind2=" " tag="720">
  1. <subfield code="a">Solinís Aspiazu, María Ángeles</subfield>
  2. <subfield code="e">author</subfield>
  </datafield>
8. <datafield ind1=" " ind2=" " tag="720">
  1. <subfield code="a">Del Pozo Rodríguez, Ana</subfield>
  2. <subfield code="e">author</subfield>
  </datafield>
9. <datafield ind1=" " ind2=" " tag="720">
  1. <subfield code="a">Rodríguez Gascón, Alicia</subfield>
  2. <subfield code="e">author</subfield>
  </datafield>
10. <datafield ind1=" " ind2=" " tag="260">
  1. <subfield code="c">2021-05-21</subfield>
  </datafield>
11. <datafield ind1=" " ind2=" " tag="520">
  1. <subfield code="a">Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</subfield>
  </datafield>
12. <datafield ind1="8" ind2=" " tag="024">
  1. <subfield code="a">Pharmaceutics 13(6) : (2021) // Article ID 771</subfield>
  </datafield>
13. <datafield ind1="8" ind2=" " tag="024">
  1. <subfield code="a">1999-4923</subfield>
  </datafield>
14. <datafield ind1="8" ind2=" " tag="024">
  1. <subfield code="a">http://hdl.handle.net/10810/52184</subfield>
  </datafield>
15. <datafield ind1="8" ind2=" " tag="024">
  1. <subfield code="a">10.3390/pharmaceutics13060771</subfield>
  </datafield>
16. <datafield ind1=" " ind2=" " tag="653">
  1. <subfield code="a">gene therapy</subfield>
  </datafield>
17. <datafield ind1=" " ind2=" " tag="653">
  1. <subfield code="a">non-viral vectors</subfield>
  </datafield>
18. <datafield ind1=" " ind2=" " tag="653">
  1. <subfield code="a">solid lipid nanoparticles</subfield>
  </datafield>
19. <datafield ind1=" " ind2=" " tag="653">
  1. <subfield code="a">pDNA</subfield>
  </datafield>
20. <datafield ind1=" " ind2=" " tag="653">
  1. <subfield code="a">Fabry disease</subfield>
  </datafield>
21. <datafield ind1=" " ind2=" " tag="653">
  1. <subfield code="a">Fabry mice</subfield>
  </datafield>
22. <datafield ind1=" " ind2=" " tag="653">
  1. <subfield code="a">α-galactosidase A</subfield>
  </datafield>
23. <datafield ind1=" " ind2=" " tag="653">
  1. <subfield code="a">intravenous administration</subfield>
  </datafield>
24. <datafield ind1="0" ind2="0" tag="245">
  1. <subfield code="a">α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</subfield>
  </datafield>
</record>

mets

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<mets ID=" DSpace_ITEM_10810-52184" OBJID=" hdl:10810/52184" PROFILE="DSpace METS SIP Profile 1.0" TYPE="DSpace ITEM" schemaLocation="http://www.loc.gov/METS/ http://www.loc.gov/standards/mets/mets.xsd">
1. <metsHdr CREATEDATE="2023-08-31T21:18:01Z">
  1. <agent ROLE="CUSTODIAN" TYPE="ORGANIZATION">
    1. <name>ADDI</name>
    </agent>
  </metsHdr>
2. <dmdSec ID="DMD_10810_52184">
  1. <mdWrap MDTYPE="MODS">
    1. <xmlData schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-1.xsd">
      1. <mods:mods schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-1.xsd">
        <mods:name>
        <mods:role>
        <mods:roleTerm type="text">author</mods:roleTerm>
        </mods:role>
        <mods:namePart>Rodríguez Castejón, Julen</mods:namePart>
        </mods:name>
        <mods:name>
        <mods:role>
        <mods:roleTerm type="text">author</mods:roleTerm>
        </mods:role>
        <mods:namePart>Alarcia Lacalle, Ana</mods:namePart>
        </mods:name>
        <mods:name>
        <mods:role>
        <mods:roleTerm type="text">author</mods:roleTerm>
        </mods:role>
        <mods:namePart>Gómez Aguado, Itziar</mods:namePart>
        </mods:name>
        <mods:name>
        <mods:role>
        <mods:roleTerm type="text">author</mods:roleTerm>
        </mods:role>
        <mods:namePart>Vicente Pascual, Mónica</mods:namePart>
        </mods:name>
        <mods:name>
        <mods:role>
        <mods:roleTerm type="text">author</mods:roleTerm>
        </mods:role>
        <mods:namePart>Solinís Aspiazu, María Ángeles</mods:namePart>
        </mods:name>
        <mods:name>
        <mods:role>
        <mods:roleTerm type="text">author</mods:roleTerm>
        </mods:role>
        <mods:namePart>Del Pozo Rodríguez, Ana</mods:namePart>
        </mods:name>
        <mods:name>
        <mods:role>
        <mods:roleTerm type="text">author</mods:roleTerm>
        </mods:role>
        <mods:namePart>Rodríguez Gascón, Alicia</mods:namePart>
        </mods:name>
        <mods:extension>
        <mods:dateAccessioned encoding="iso8601">2021-07-08T16:39:17Z</mods:dateAccessioned>
        </mods:extension>
        <mods:extension>
        <mods:dateAvailable encoding="iso8601">2021-07-08T16:39:17Z</mods:dateAvailable>
        </mods:extension>
        <mods:originInfo>
        <mods:dateIssued encoding="iso8601">2021-05-21</mods:dateIssued>
        </mods:originInfo>
        <mods:identifier type="citation">Pharmaceutics 13(6) : (2021) // Article ID 771</mods:identifier>
        <mods:identifier type="issn">1999-4923</mods:identifier>
        <mods:identifier type="uri">http://hdl.handle.net/10810/52184</mods:identifier>
        <mods:identifier type="doi">10.3390/pharmaceutics13060771</mods:identifier>
        <mods:abstract>Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</mods:abstract>
        <mods:language>
        <mods:languageTerm authority="rfc3066">eng</mods:languageTerm>
        </mods:language>
        <mods:accessCondition type="useAndReproduction">info:eu-repo/semantics/openAccess</mods:accessCondition>
        <mods:subject>
        <mods:topic>gene therapy</mods:topic>
        </mods:subject>
        <mods:subject>
        <mods:topic>non-viral vectors</mods:topic>
        </mods:subject>
        <mods:subject>
        <mods:topic>solid lipid nanoparticles</mods:topic>
        </mods:subject>
        <mods:subject>
        <mods:topic>pDNA</mods:topic>
        </mods:subject>
        <mods:subject>
        <mods:topic>Fabry disease</mods:topic>
        </mods:subject>
        <mods:subject>
        <mods:topic>Fabry mice</mods:topic>
        </mods:subject>
        <mods:subject>
        <mods:topic>α-galactosidase A</mods:topic>
        </mods:subject>
        <mods:subject>
        <mods:topic>intravenous administration</mods:topic>
        </mods:subject>
        <mods:titleInfo>
        <mods:title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</mods:title>
        </mods:titleInfo>
        <mods:genre>info:eu-repo/semantics/article</mods:genre>
        </mods:mods>
      </xmlData>
    </mdWrap>
  </dmdSec>
3. <amdSec ID="TMD_10810_52184">
  1. <rightsMD ID="RIG_10810_52184">
    1. <mdWrap MDTYPE="OTHER" MIMETYPE="text/plain" OTHERMDTYPE="DSpaceDepositLicense">
      1. <binData>TElDRU5DSUEgREUgVVNPIERFIERFUkVDSE9TIC1DRVNJw5NOIE5PIEVYQ0xVU0lWQS0gUEFSQSBBVVRPQVJDSElWTyBERSBNQVRFUklBTCBFTiBFTCAKQVJDSElWTyBESUdJVEFMIFBBUkEgTEEgRE9DRU5DSUEgWSBMQSBJTlZFU1RJR0FDScOTTiAoQURESSkgREUgTEEgVU5JVkVSU0lEQUQgREVMIFBBw41TIFZBU0NPLiAKClBhcmEgcXVlIGxhIFVuaXZlcnNpZGFkIGRlbCBQYcOtcyBWYXNjbyBwdWVkYSByZXByb2R1Y2lyLCB0cmFuc2Zvcm1hciwgZGlzdHJpYnVpciB5IApjb211bmljYXIgcMO6YmxpY2FtZW50ZSBlbCBtYXRlcmlhbCBkZXBvc2l0YWRvIGVuIGVzdGUgQXJjaGl2byBEaWdpdGFsLCBlcyBuZWNlc2FyaW8Kc3UgYWN1ZXJkbyB5IGFjZXB0YWNpw7NuIGEgbG9zIHTDqXJtaW5vcyBkZSBFU1RBIExJQ0VOQ0lBLiAKClBvciBmYXZvciwgbMOpYWxhIGNvbiBkZXRlbmltaWVudG8uIFN1IGFwcm9iYWNpw7NuIG1lZGlhbnRlIHVuIGNsaWMgZW4gZWwgYm90w7NuIEFDRVBUTyBMQSAKTElDRU5DSUEgZXhwcmVzYSBzdSBjb25zZW50aW1pZW50byBlbiBsb3MgdMOpcm1pbm9zIGluZGljYWRvcyBhIGNvbnRpbnVhY2nDs24uCgpNZWRpYW50ZSBsYSBhY2VwdGFjacOzbiBkZSBlc3RhIGxpY2VuY2lhLCBVc3RlZCwgQVVUT1IgZGVsIG1hdGVyaWFsIGRlcG9zaXRhZG8sIG90b3JnYSBhIGxhIApVbml2ZXJzaWRhZCBkZWwgUGHDrXMgVmFzY28sIGxhIGF1dG9yaXphY2nDs24gZGUgdXNvIG8gY2VzacOzbiBOTyBFWENMVVNJVkEsIGdyYXR1aXRhLCAKY29uIMOhbWJpdG8gbXVuZGlhbCB5IHBvciBlbCBwbGF6byBtw6F4aW1vIGxlZ2FsLCBkZSBsb3MgZGVyZWNob3MgZGUgcmVwcm9kdWNjacOzbiwgCmRpc3RyaWJ1Y2nDs24sIGNvbXVuaWNhY2nDs24gcMO6YmxpY2EgLWluY2x1aWRvIGVsIGRlcmVjaG8gZGUgcHVlc3RhIGEgZGlzcG9zaWNpw7NuIAplbGVjdHLDs25pY2EtIHkgdHJhbnNmb3JtYWNpw7NuIHNvYnJlIGRpY2hvIG1hdGVyaWFsLCBwZXJtaXRpZW5kbyBzZSBwb25nYSBhIGRpc3Bvc2ljacOzbiAKZGUgdGVyY2Vyb3MgdXN1YXJpb3MgZGVsIEFyY2hpdm8gRGlnaXRhbCBBRERJIGNvbiBsb3MgdXNvcyBwZXJtaXRpZG9zIHkgY29uZGljaW9uZXMgZGUgCnVzbyBxdWUgc2UgZXN0YWJsZWNlbiBlbiBsYSBsaWNlbmNpYSBDcmVhdGl2ZSBDb21tb25zIGFzb2NpYWRhIGEgZXN0ZSBkZXDDs3NpdG8sIGRlIG1vZG8gCnF1ZSBlbCBtYXRlcmlhbCBwdWVkYSBzZXIgZGlzdHJpYnVpZG8sIGNvcGlhZG8geSBleGhpYmlkbyBzaWVtcHJlIHF1ZSBzZSBjaXRlIHN1IGF1dG9yw61hLCAKbm8gc2Ugb2J0ZW5nYSBiZW5lZmljaW8gY29tZXJjaWFsLCB5IG5vIHNlIHJlYWxpY2VuIG9icmFzIGRlcml2YWRhcy4gCgpVc3RlZCBBQ0VQVEEgcXVlIGxhIFVuaXZlcnNpZGFkIGRlbCBQYcOtcyBWYXNjbyBwdWVkYSwgc2luIGFsdGVyYXIgZWwgY29udGVuaWRvLCB0cmFuc2Zvcm1hciAKbyBhZGFwdGFyIGVsIG1hdGVyaWFsIGRlcG9zaXRhZG8gYSBjdWFscXVpZXIgb3RybyBmb3JtYXRvIG8gbWVkaW8gcXVlIHJlc3VsdGUgbmVjZXNhcmlvIGNvbiBmaW5lcyAKZGUgcHJlc2VydmFjacOzbi4gSWd1YWxtZW50ZSBBQ0VQVEEgcXVlIGxhIFVuaXZlcnNpZGFkIGRlbCBQYcOtcyBWYXNjbyBwdWVkYSBndWFyZGFyIG3DoXMgCmRlIHVuYSBjb3BpYSBkZWwgbWF0ZXJpYWwgZGVwb3NpdGFkbyBhIGZpbiBkZSByZWFsaXphciBjb3BpYXMgZGUgc2VndXJpZGFkIHkgcHJlc2VydmFyIGVsIAptYXRlcmlhbCBwYXJhIGVsIGZ1dHVyby4KClVzdGVkIEFTRUdVUkEgeSBHQVJBTlRJWkEgcXVlIGVsIG1hdGVyaWFsIGRlcG9zaXRhZG8gZXMgdW5hIG9icmEgb3JpZ2luYWwgZGUgc3UgY3JlYWNpw7NuIHkgCnNvYnJlIGxhIHF1ZSBVc3RlZCBvc3RlbnRhIGxhIHRpdHVsYXJpZGFkIGRlIGRlcmVjaG9zIGRlIGF1dG9yIG5lY2VzYXJpYSBwYXJhIG90b3JnYXIgbGEgY2VzacOzbiAKY29udGVuaWRhIGVuIGxhIHByZXNlbnRlIExpY2VuY2lhLiBFbiBjYXNvIGRlIGNvdGl0dWxhcmlkYWQgVXN0ZWQgZGVjbGFyYSBxdWUgY3VlbnRhIGNvbiBlbCAKY29uc2VudGltaWVudG8gZGUgbG9zIHJlc3RhbnRlcyB0aXR1bGFyZXMgcGFyYSBvdG9yZ2FyIGxhIHByZXNlbnRlIGxpY2VuY2lhLiBZIGVuIGVsIGNhc28gZGUgcHJldmlhIApjZXNpw7NuIGRlIGRlcmVjaG9zIGEgdGVyY2Vyb3MgVXN0ZWQgZGVjbGFyYSBxdWUgY3VlbnRhIGNvbiBzdSBhdXRvcml6YWNpw7NuIG8gYmllbiBxdWUgCnJldGllbmUgbGEgZmFjdWx0YWQgZGUgaGFjZXIgdXNvIGRlIGVzdG9zIGRlcmVjaG9zIGVuIGxhIGZvcm1hIHByZXZpc3RhIGVuIGxhIHByZXNlbnRlIGxpY2VuY2lhLiAKCkVuIGNvbnNlY3VlbmNpYSwgVXN0ZWQgQVNFR1VSQSB5IEdBUkFOVElaQSBxdWUgZWwgbWF0ZXJpYWwgcXVlIHNlIGRlcG9zaXRhIGVuIGVsIEFyY2hpdm8gCkRpZ2l0YWwgQURESSBkZSBsYSBVbml2ZXJzaWRhZCBkZWwgUGHDrXMgVmFzY28gTk8gSU5GUklOR0UgZGVyZWNobyBhbGd1bm8gYSB0ZXJjZXJvcywKeWEgc2VhIGRlIHByb3BpZWRhZCBpbnRlbGVjdHVhbCBvIGluZHVzdHJpYWwsIGRlcmVjaG8gYWwgaG9ub3IsIGEgbGEgaW50aW1pZGFkIHkgYSBsYSBpbWFnZW4sIApvIGN1YWxxdWllciBvdHJvIGRlcmVjaG8uCgpFbiBlbCBjYXNvIGRlIHF1ZSBlbCBtYXRlcmlhbCBkZXBvc2l0YWRvIGNvbnR1dmllcmEgb3RybyBtYXRlcmlhbCBkZWwgcXVlIFVzdGVkIG5vIGVzIGVsIHRpdHVsYXIKZGUgbG9zIGRlcmVjaG9zIGRlIGF1dG9yLCBVc3RlZCBBU0VHVVJBIHkgR0FSQU5USVpBIGhhYmVyIG9idGVuaWRvIGxhIGltcHJlc2NpbmRpYmxlIGF1dG9yaXphY2nDs24KZGVsIGNvcnJlc3BvbmRpZW50ZSB0aXR1bGFyIGRlIG1vZG8gcXVlIHNlYSBwb3NpYmxlIHBhcmEgVXN0ZWQgb3RvcmdhciBsYSBwcmVzZW50ZSBMaWNlbmNpYTsgCmFzw60gbWlzbW8gVXN0ZWQgQVNFR1VSQSB5IEdBUkFOVElaQSBxdWUgZGljaG8gdGVyY2VybyB0aXR1bGFyIGRlIGRlcmVjaG9zIGRlIGF1dG9yIHF1ZWRhIAppZGVudGlmaWNhZG8geSByZWNvbm9jaWRvIGNvbW8gdGFsIGVuIGVsIGNvbnRlbmlkbyBkZWwgbWF0ZXJpYWwgZGVwb3NpdGFkby4KCkxhIFVuaXZlcnNpZGFkIGRlbCBQYcOtcyBWYXNjbyBhZHF1aWVyZSBlbCBjb21wcm9taXNvIGRlIGlkZW50aWZpY2FybGUgYSBVc3RlZCBjb21vIGF1dG9yIApvIHRpdHVsYXIgZGUgZGVyZWNob3MgZGUgYXV0b3IgZGVsIG1hdGVyaWFsIGRlcG9zaXRhZG8sIHkgbm8gZWZlY3R1YXLDoSBtw6FzIGFsdGVyYWNpb25lcyAKZW4gZGljaG8gbWF0ZXJpYWwgcXVlIGxhcyBleHByZXNhbWVudGUgcGVybWl0aWRhcyBlbiBlc3RhIExpY2VuY2lhLiAKClVzdGVkIHBvZHLDoSBzb2xpY2l0YXIgbGEgcmV0aXJhZGEgZGUgbGEgb2JyYSBkZWwgQXJjaGl2byBBRERJIHBvciBjYXVzYSBqdXN0aWZpY2FkYS4KQSB0YWwgZmluIGRlYmVyw6EgcG9uZXJzZSBlbiBjb250YWN0byBjb24gZWwgcmVzcG9uc2FibGUgZGVsIG1pc21vLiBEZSBpZ3VhbCBtb2RvIEFEREkgCnBvZHLDoSByZXRpcmFyIGVsIG1hdGVyaWFsLCBwcmV2aWEgbm90aWZpY2FjacOzbiwgZW4gc3VwdWVzdG9zIHN1ZmljaWVudGVtZW50ZSAKanVzdGlmaWNhZG9zLCBvIGVuIGNhc28gZGUgcmVjbGFtYWNpb25lcyBkZSB0ZXJjZXJvcy4gCgpVc3RlZCBzZXLDoSBjb252ZW5pZW50ZW1lbnRlIG5vdGlmaWNhZG8gZGUgY3VhbHF1aWVyIHJlY2xhbWFjacOzbiBxdWUgcHVlZGFuIGZvcm11bGFyCnRlcmNlcmFzIHBlcnNvbmFzIGVuIHJlbGFjacOzbiBjb24gbGEgb2JyYSB5LCBlbiBwYXJ0aWN1bGFyLCBkZSByZWNsYW1hY2lvbmVzIHJlbGF0aXZhcwphIGxvcyBkZXJlY2hvcyBkZSBwcm9waWVkYWQgaW50ZWxlY3R1YWwgc29icmUgZWxsYS4gCgo=</binData>
      </mdWrap>
    </rightsMD>
  </amdSec>
4. <amdSec ID="FO_10810_52184_1">
  1. <techMD ID="TECH_O_10810_52184_1">
    1. <mdWrap MDTYPE="PREMIS">
      1. <xmlData schemaLocation="http://www.loc.gov/standards/premis http://www.loc.gov/standards/premis/PREMIS-v1-0.xsd">
        <premis:premis>
        <premis:object>
        <premis:objectIdentifier>
        <premis:objectIdentifierType>URL</premis:objectIdentifierType>
        <premis:objectIdentifierValue>http://addi.ehu.es/bitstream/10810/52184/1/pharmaceutics-13-00771-v2.pdf</premis:objectIdentifierValue>
        </premis:objectIdentifier>
        <premis:objectCategory>File</premis:objectCategory>
        <premis:objectCharacteristics>
        <premis:fixity>
        <premis:messageDigestAlgorithm>MD5</premis:messageDigestAlgorithm>
        <premis:messageDigest>a559d129762e0e9db8f71dd05212f44a</premis:messageDigest>
        </premis:fixity>
        <premis:size>1420923</premis:size>
        <premis:format>
        <premis:formatDesignation>
        <premis:formatName>application/pdf</premis:formatName>
        </premis:formatDesignation>
        </premis:format>
        </premis:objectCharacteristics>
        <premis:originalName>pharmaceutics-13-00771-v2.pdf</premis:originalName>
        </premis:object>
        </premis:premis>
        </xmlData>
      </mdWrap>
    </techMD>
  </amdSec>
5. <amdSec ID="FT_10810_52184_4">
  1. <techMD ID="TECH_T_10810_52184_4">
    1. <mdWrap MDTYPE="PREMIS">
      1. <xmlData schemaLocation="http://www.loc.gov/standards/premis http://www.loc.gov/standards/premis/PREMIS-v1-0.xsd">
        <premis:premis>
        <premis:object>
        <premis:objectIdentifier>
        <premis:objectIdentifierType>URL</premis:objectIdentifierType>
        <premis:objectIdentifierValue>http://addi.ehu.es/bitstream/10810/52184/4/pharmaceutics-13-00771-v2.pdf.txt</premis:objectIdentifierValue>
        </premis:objectIdentifier>
        <premis:objectCategory>File</premis:objectCategory>
        <premis:objectCharacteristics>
        <premis:fixity>
        <premis:messageDigestAlgorithm>MD5</premis:messageDigestAlgorithm>
        <premis:messageDigest>69382e02720acd3fe0bcd3b71caa0f86</premis:messageDigest>
        </premis:fixity>
        <premis:size>56103</premis:size>
        <premis:format>
        <premis:formatDesignation>
        <premis:formatName>text/plain</premis:formatName>
        </premis:formatDesignation>
        </premis:format>
        </premis:objectCharacteristics>
        <premis:originalName>pharmaceutics-13-00771-v2.pdf.txt</premis:originalName>
        </premis:object>
        </premis:premis>
        </xmlData>
      </mdWrap>
    </techMD>
  </amdSec>
6. <fileSec>
  1. <fileGrp USE="ORIGINAL">
    1. <file ADMID="FO_10810_52184_1" CHECKSUM="a559d129762e0e9db8f71dd05212f44a" CHECKSUMTYPE="MD5" GROUPID="GROUP_BITSTREAM_10810_52184_1" ID="BITSTREAM_ORIGINAL_10810_52184_1" MIMETYPE="application/pdf" SEQ="1" SIZE="1420923">
      1. <FLocat LOCTYPE="URL" href="http://addi.ehu.es/bitstream/10810/52184/1/pharmaceutics-13-00771-v2.pdf" type="simple" />
      </file>
    </fileGrp>
  2. <fileGrp USE="TEXT">
    1. <file ADMID="FT_10810_52184_4" CHECKSUM="69382e02720acd3fe0bcd3b71caa0f86" CHECKSUMTYPE="MD5" GROUPID="GROUP_BITSTREAM_10810_52184_4" ID="BITSTREAM_TEXT_10810_52184_4" MIMETYPE="text/plain" SEQ="4" SIZE="56103">
      1. <FLocat LOCTYPE="URL" href="http://addi.ehu.es/bitstream/10810/52184/4/pharmaceutics-13-00771-v2.pdf.txt" type="simple" />
      </file>
    </fileGrp>
  </fileSec>
7. <structMap LABEL="DSpace Object" TYPE="LOGICAL">
  1. <div ADMID="DMD_10810_52184" TYPE="DSpace Object Contents">
    1. <div TYPE="DSpace BITSTREAM">
      1. <fptr FILEID="BITSTREAM_ORIGINAL_10810_52184_1" />
      </div>
    </div>
  </structMap>
</mets>

mods

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<mods:mods schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-1.xsd">
1. <mods:name>
  1. <mods:namePart>Rodríguez Castejón, Julen</mods:namePart>
  </mods:name>
2. <mods:name>
  1. <mods:namePart>Alarcia Lacalle, Ana</mods:namePart>
  </mods:name>
3. <mods:name>
  1. <mods:namePart>Gómez Aguado, Itziar</mods:namePart>
  </mods:name>
4. <mods:name>
  1. <mods:namePart>Vicente Pascual, Mónica</mods:namePart>
  </mods:name>
5. <mods:name>
  1. <mods:namePart>Solinís Aspiazu, María Ángeles</mods:namePart>
  </mods:name>
6. <mods:name>
  1. <mods:namePart>Del Pozo Rodríguez, Ana</mods:namePart>
  </mods:name>
7. <mods:name>
  1. <mods:namePart>Rodríguez Gascón, Alicia</mods:namePart>
  </mods:name>
8. <mods:extension>
  1. <mods:dateAvailable encoding="iso8601">2021-07-08T16:39:17Z</mods:dateAvailable>
  </mods:extension>
9. <mods:extension>
  1. <mods:dateAccessioned encoding="iso8601">2021-07-08T16:39:17Z</mods:dateAccessioned>
  </mods:extension>
10. <mods:originInfo>
  1. <mods:dateIssued encoding="iso8601">2021-05-21</mods:dateIssued>
  </mods:originInfo>
11. <mods:identifier type="citation">Pharmaceutics 13(6) : (2021) // Article ID 771</mods:identifier>
12. <mods:identifier type="issn">1999-4923</mods:identifier>
13. <mods:identifier type="uri">http://hdl.handle.net/10810/52184</mods:identifier>
14. <mods:identifier type="doi">10.3390/pharmaceutics13060771</mods:identifier>
15. <mods:abstract>Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</mods:abstract>
16. <mods:language>
  1. <mods:languageTerm>eng</mods:languageTerm>
  </mods:language>
17. <mods:accessCondition type="useAndReproduction">http://creativecommons.org/licenses/by/3.0/es/</mods:accessCondition>
18. <mods:accessCondition type="useAndReproduction">© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</mods:accessCondition>
19. <mods:accessCondition type="useAndReproduction">info:eu-repo/semantics/openAccess</mods:accessCondition>
20. <mods:subject>
  1. <mods:topic>gene therapy</mods:topic>
  </mods:subject>
21. <mods:subject>
  1. <mods:topic>non-viral vectors</mods:topic>
  </mods:subject>
22. <mods:subject>
  1. <mods:topic>solid lipid nanoparticles</mods:topic>
  </mods:subject>
23. <mods:subject>
  1. <mods:topic>pDNA</mods:topic>
  </mods:subject>
24. <mods:subject>
  1. <mods:topic>Fabry disease</mods:topic>
  </mods:subject>
25. <mods:subject>
  1. <mods:topic>Fabry mice</mods:topic>
  </mods:subject>
26. <mods:subject>
  1. <mods:topic>α-galactosidase A</mods:topic>
  </mods:subject>
27. <mods:subject>
  1. <mods:topic>intravenous administration</mods:topic>
  </mods:subject>
28. <mods:titleInfo>
  1. <mods:title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</mods:title>
  </mods:titleInfo>
29. <mods:genre>info:eu-repo/semantics/article</mods:genre>
</mods:mods>

oaire

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<oaire:record schemaLocation="http://namespaceopenaire.eu/schema/oaire/">
1. <dc:title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</dc:title>
2. <datacite:creator>
  1. <datacite:creatorName>Rodríguez Castejón, Julen</datacite:creatorName>
  </datacite:creator>
3. <datacite:creator>
  1. <datacite:creatorName>Alarcia Lacalle, Ana</datacite:creatorName>
  </datacite:creator>
4. <datacite:creator>
  1. <datacite:creatorName>Gómez Aguado, Itziar</datacite:creatorName>
  </datacite:creator>
5. <datacite:creator>
  1. <datacite:creatorName>Vicente Pascual, Mónica</datacite:creatorName>
  </datacite:creator>
6. <datacite:creator>
  1. <datacite:creatorName>Solinís Aspiazu, María Ángeles</datacite:creatorName>
  </datacite:creator>
7. <datacite:creator>
  1. <datacite:creatorName>Del Pozo Rodríguez, Ana</datacite:creatorName>
  </datacite:creator>
8. <datacite:creator>
  1. <datacite:creatorName>Rodríguez Gascón, Alicia</datacite:creatorName>
  </datacite:creator>
9. <dc:subject>gene therapy</dc:subject>
10. <dc:subject>non-viral vectors</dc:subject>
11. <dc:subject>solid lipid nanoparticles</dc:subject>
12. <dc:subject>pDNA</dc:subject>
13. <dc:subject>Fabry disease</dc:subject>
14. <dc:subject>Fabry mice</dc:subject>
15. <dc:subject>α-galactosidase A</dc:subject>
16. <dc:subject>intravenous administration</dc:subject>
17. <dc:description>Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</dc:description>
18. <dc:description>This research was funded by Merck Salud Foundation, MCIU/AEI/FEDER, UE (RTI2018-098672-B-I00) and by the University of the Basque Country UPV/EHU (GIU17/032).</dc:description>
19. <dc:date>2021-07-08T16:39:17Z</dc:date>
20. <dc:date>2021-07-08T16:39:17Z</dc:date>
21. <dc:date>2021-05-21</dc:date>
22. <dc:date>2021-06-24T14:11:30Z</dc:date>
23. <dc:type>info:eu-repo/semantics/article</dc:type>
24. <datacite:alternateIdentifier>Pharmaceutics 13(6) : (2021) // Article ID 771</datacite:alternateIdentifier>
25. <datacite:alternateIdentifier>1999-4923</datacite:alternateIdentifier>
26. <datacite:alternateIdentifier>http://hdl.handle.net/10810/52184</datacite:alternateIdentifier>
27. <datacite:alternateIdentifier>10.3390/pharmaceutics13060771</datacite:alternateIdentifier>
28. <dc:language>eng</dc:language>
29. <dc:relation>info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</dc:relation>
30. <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
31. <dc:rights>http://creativecommons.org/licenses/by/3.0/es/</dc:rights>
32. <dc:rights>© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</dc:rights>
33. <dc:format>application/pdf</dc:format>
34. <dc:publisher>MDPI</dc:publisher>
35. <oaire:file>http://addi.ehu.es/bitstream/10810/52184/1/pharmaceutics-13-00771-v2.pdf</oaire:file>
</oaire:record>

ore

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<atom:entry schemaLocation="http://www.w3.org/2005/Atom http://www.kbcafe.com/rss/atom.xsd.xml">
1. <atom:id>http://hdl.handle.net/10810/52184/ore.xml</atom:id>
2. <atom:link href="http://hdl.handle.net/10810/52184" rel="alternate" />
3. <atom:link href="http://hdl.handle.net/10810/52184/ore.xml" rel="http://www.openarchives.org/ore/terms/describes" />
4. <atom:link href="http://hdl.handle.net/10810/52184/ore.xml#atom" rel="self" type="application/atom+xml" />
5. <atom:published>2021-07-08T16:39:17Z</atom:published>
6. <atom:updated>2021-07-08T16:39:17Z</atom:updated>
7. <atom:source>
  1. <atom:generator>ADDI</atom:generator>
  </atom:source>
8. <atom:title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</atom:title>
9. <atom:author>
  1. <atom:name>Rodríguez Castejón, Julen</atom:name>
  </atom:author>
10. <atom:author>
  1. <atom:name>Alarcia Lacalle, Ana</atom:name>
  </atom:author>
11. <atom:author>
  1. <atom:name>Gómez Aguado, Itziar</atom:name>
  </atom:author>
12. <atom:author>
  1. <atom:name>Vicente Pascual, Mónica</atom:name>
  </atom:author>
13. <atom:author>
  1. <atom:name>Solinís Aspiazu, María Ángeles</atom:name>
  </atom:author>
14. <atom:author>
  1. <atom:name>Del Pozo Rodríguez, Ana</atom:name>
  </atom:author>
15. <atom:author>
  1. <atom:name>Rodríguez Gascón, Alicia</atom:name>
  </atom:author>
16. <atom:category label="Aggregation" scheme="http://www.openarchives.org/ore/terms/" term="http://www.openarchives.org/ore/terms/Aggregation" />
17. <atom:category scheme="http://www.openarchives.org/ore/atom/modified" term="2021-07-08T16:39:17Z" />
18. <atom:category label="DSpace Item" scheme="http://www.dspace.org/objectModel/" term="DSpaceItem" />
19. <atom:link href="http://addi.ehu.es/bitstream/10810/52184/1/pharmaceutics-13-00771-v2.pdf" length="1420923" rel="http://www.openarchives.org/ore/terms/aggregates" title="pharmaceutics-13-00771-v2.pdf" type="application/pdf" />
20. <oreatom:triples>
  1. <rdf:Description about="http://hdl.handle.net/10810/52184/ore.xml#atom">
    1. <rdf:type resource="http://www.dspace.org/objectModel/DSpaceItem" />
    2. <dcterms:modified>2021-07-08T16:39:17Z</dcterms:modified>
    </rdf:Description>
  2. <rdf:Description about="http://addi.ehu.es/bitstream/10810/52184/4/pharmaceutics-13-00771-v2.pdf.txt">
    1. <rdf:type resource="http://www.dspace.org/objectModel/DSpaceBitstream" />
    2. <dcterms:description>TEXT</dcterms:description>
    </rdf:Description>
  3. <rdf:Description about="http://addi.ehu.es/bitstream/10810/52184/1/pharmaceutics-13-00771-v2.pdf">
    1. <rdf:type resource="http://www.dspace.org/objectModel/DSpaceBitstream" />
    2. <dcterms:description>ORIGINAL</dcterms:description>
    </rdf:Description>
  4. <rdf:Description about="http://addi.ehu.es/bitstream/10810/52184/2/license.txt">
    1. <rdf:type resource="http://www.dspace.org/objectModel/DSpaceBitstream" />
    2. <dcterms:description>LICENSE</dcterms:description>
    </rdf:Description>
  5. <rdf:Description about="http://addi.ehu.es/bitstream/10810/52184/3/packager-60d49291.zip">
    1. <rdf:type resource="http://www.dspace.org/objectModel/DSpaceBitstream" />
    2. <dcterms:description>SWORD</dcterms:description>
    </rdf:Description>
  </oreatom:triples>
</atom:entry>

qdc

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<qdc:qualifieddc schemaLocation="http://dublincore.org/schemas/xmls/qdc/2008/02/11 dcterms.xsd">
1. <dc:title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</dc:title>
2. <dc:creator>Rodríguez Castejón, Julen</dc:creator>
3. <dc:creator>Alarcia Lacalle, Ana</dc:creator>
4. <dc:creator>Gómez Aguado, Itziar</dc:creator>
5. <dc:creator>Vicente Pascual, Mónica</dc:creator>
6. <dc:creator>Solinís Aspiazu, María Ángeles</dc:creator>
7. <dc:creator>Del Pozo Rodríguez, Ana</dc:creator>
8. <dc:creator>Rodríguez Gascón, Alicia</dc:creator>
9. <dc:contributor>Farmacia y ciencias de los alimentos</dc:contributor>
10. <dc:contributor>Farmazia eta elikagaien zientziak</dc:contributor>
11. <dc:coverage>This research was funded by Merck Salud Foundation, MCIU/AEI/FEDER, UE (RTI2018-098672-B-I00) and by the University of the Basque Country UPV/EHU (GIU17/032).</dc:coverage>
12. <dc:subject>gene therapy</dc:subject>
13. <dc:subject>non-viral vectors</dc:subject>
14. <dc:subject>solid lipid nanoparticles</dc:subject>
15. <dc:subject>pDNA</dc:subject>
16. <dc:subject>Fabry disease</dc:subject>
17. <dc:subject>Fabry mice</dc:subject>
18. <dc:subject>α-galactosidase A</dc:subject>
19. <dc:subject>intravenous administration</dc:subject>
20. <dcterms:abstract>Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</dcterms:abstract>
21. <dcterms:issued>2021-05-21</dcterms:issued>
22. <dc:type>info:eu-repo/semantics/article</dc:type>
23. <dc:identifier>http://hdl.handle.net/10810/52184</dc:identifier>
24. <dcterms:bibliographicCitation>Pharmaceutics 13(6) : (2021) // Article ID 771</dcterms:bibliographicCitation>
25. <dcterms:bibliographicCitation>10.3390/pharmaceutics13060771</dcterms:bibliographicCitation>
26. <dc:relation>1999-4923</dc:relation>
27. <dc:language>eng</dc:language>
28. <dc:relation>https://www.mdpi.com/1999-4923/13/6/771</dc:relation>
29. <dc:relation>info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</dc:relation>
30. <dcterms:rightsHolder>© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</dcterms:rightsHolder>
31. <dcterms:license>http://creativecommons.org/licenses/by/3.0/es/</dcterms:license>
32. <dcterms:accessRights>info:eu-repo/semantics/openAccess</dcterms:accessRights>
33. <dc:publisher>MDPI</dc:publisher>
</qdc:qualifieddc>

rdf

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<rdf:RDF schemaLocation="http://www.openarchives.org/OAI/2.0/rdf/ http://www.openarchives.org/OAI/2.0/rdf.xsd">
1. <ow:Publication about="oai:addi.ehu.eus:10810/52184">
  1. <dc:title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</dc:title>
  2. <dc:creator>Rodríguez Castejón, Julen</dc:creator>
  3. <dc:creator>Alarcia Lacalle, Ana</dc:creator>
  4. <dc:creator>Gómez Aguado, Itziar</dc:creator>
  5. <dc:creator>Vicente Pascual, Mónica</dc:creator>
  6. <dc:creator>Solinís Aspiazu, María Ángeles</dc:creator>
  7. <dc:creator>Del Pozo Rodríguez, Ana</dc:creator>
  8. <dc:creator>Rodríguez Gascón, Alicia</dc:creator>
  9. <dc:subject>gene therapy</dc:subject>
  10. <dc:subject>non-viral vectors</dc:subject>
  11. <dc:subject>solid lipid nanoparticles</dc:subject>
  12. <dc:subject>pDNA</dc:subject>
  13. <dc:subject>Fabry disease</dc:subject>
  14. <dc:subject>Fabry mice</dc:subject>
  15. <dc:subject>α-galactosidase A</dc:subject>
  16. <dc:subject>intravenous administration</dc:subject>
  17. <dc:description>Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</dc:description>
  18. <dc:date>2021-07-08T16:39:17Z</dc:date>
  19. <dc:date>2021-07-08T16:39:17Z</dc:date>
  20. <dc:date>2021-05-21</dc:date>
  21. <dc:date>2021-06-24T14:11:30Z</dc:date>
  22. <dc:type>info:eu-repo/semantics/article</dc:type>
  23. <dc:identifier>Pharmaceutics 13(6) : (2021) // Article ID 771</dc:identifier>
  24. <dc:identifier>1999-4923</dc:identifier>
  25. <dc:identifier>http://hdl.handle.net/10810/52184</dc:identifier>
  26. <dc:identifier>10.3390/pharmaceutics13060771</dc:identifier>
  27. <dc:language>eng</dc:language>
  28. <dc:relation>https://www.mdpi.com/1999-4923/13/6/771</dc:relation>
  29. <dc:relation>info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</dc:relation>
  30. <dc:rights>http://creativecommons.org/licenses/by/3.0/es/</dc:rights>
  31. <dc:rights>© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</dc:rights>
  32. <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  33. <dc:publisher>MDPI</dc:publisher>
  </ow:Publication>
</rdf:RDF>

repec

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<qdc:qualifieddc schemaLocation="http://purl.org/dc/elements/1.1/ http://dublincore.org/schemas/xmls/qdc/2006/01/06/dc.xsd http://purl.org/dc/terms/ http://dublincore.org/schemas/xmls/qdc/2006/01/06/dcterms.xsd http://dspace.org/qualifieddc/ http://www.ukoln.ac.uk/metadata/dcmi/xmlschema/qualifieddc.xsd">
1. <dc:title>α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</dc:title>
2. <dc:creator>Rodríguez Castejón, Julen</dc:creator>
3. <dc:creator>Alarcia Lacalle, Ana</dc:creator>
4. <dc:creator>Gómez Aguado, Itziar</dc:creator>
5. <dc:creator>Vicente Pascual, Mónica</dc:creator>
6. <dc:creator>Solinís Aspiazu, María Ángeles</dc:creator>
7. <dc:creator>Del Pozo Rodríguez, Ana</dc:creator>
8. <dc:creator>Rodríguez Gascón, Alicia</dc:creator>
9. <dc:subject>gene therapy</dc:subject>
10. <dc:subject>non-viral vectors</dc:subject>
11. <dc:subject>solid lipid nanoparticles</dc:subject>
12. <dc:subject>pDNA</dc:subject>
13. <dc:subject>Fabry disease</dc:subject>
14. <dc:subject>Fabry mice</dc:subject>
15. <dc:subject>α-galactosidase A</dc:subject>
16. <dc:subject>intravenous administration</dc:subject>
17. <dcterms:abstract>Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</dcterms:abstract>
18. <dcterms:dateAccepted>2021-07-08T16:39:17Z</dcterms:dateAccepted>
19. <dcterms:available>2021-07-08T16:39:17Z</dcterms:available>
20. <dcterms:created>2021-07-08T16:39:17Z</dcterms:created>
21. <dcterms:issued>2021-05-21</dcterms:issued>
22. <dc:type>info:eu-repo/semantics/article</dc:type>
23. <dc:identifier>Pharmaceutics 13(6) : (2021) // Article ID 771</dc:identifier>
24. <dc:identifier>1999-4923</dc:identifier>
25. <dc:identifier>http://hdl.handle.net/10810/52184</dc:identifier>
26. <dc:identifier>10.3390/pharmaceutics13060771</dc:identifier>
27. <dc:language>eng</dc:language>
28. <dc:relation>https://www.mdpi.com/1999-4923/13/6/771</dc:relation>
29. <dc:relation>info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</dc:relation>
30. <dc:rights>http://creativecommons.org/licenses/by/3.0/es/</dc:rights>
31. <dc:rights>© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</dc:rights>
32. <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
33. <dc:publisher>MDPI</dc:publisher>
</qdc:qualifieddc>

xoai

Deskargatu XML

<?xml version="1.0" encoding="UTF-8" ?>

<metadata schemaLocation="http://www.lyncode.com/xoai http://www.lyncode.com/xsd/xoai.xsd">
1. <element name="dc">
  1. <element name="contributor">
    1. <element name="author">
      1. <element name="none">
        <field name="value">Rodríguez Castejón, Julen</field>
        <field name="authority">14cefb36-55d4-470d-b67e-16171ca4e8ec</field>
        <field name="confidence">600</field>
        <field name="value">Alarcia Lacalle, Ana</field>
        <field name="value">Gómez Aguado, Itziar</field>
        <field name="authority">bc069c0f-cc81-48db-8821-6c63754084c5</field>
        <field name="confidence">600</field>
        <field name="value">Vicente Pascual, Mónica</field>
        <field name="value">Solinís Aspiazu, María Ángeles</field>
        <field name="authority">91649621-546b-4ecd-a219-4cc1b801a451</field>
        <field name="confidence">600</field>
        <field name="value">Del Pozo Rodríguez, Ana</field>
        <field name="authority">06123ee8-8fcd-4596-a206-27c2dfa8af04</field>
        <field name="confidence">600</field>
        <field name="value">Rodríguez Gascón, Alicia</field>
        <field name="authority">3467a71f-4ba6-4b7b-8a7b-d391a93df83e</field>
        <field name="confidence">600</field>
        </element>
      </element>
    </element>
  2. <element name="date">
    1. <element name="accessioned">
      1. <element name="none">
        <field name="value">2021-07-08T16:39:17Z</field>
        </element>
      </element>
    2. <element name="available">
      1. <element name="none">
        <field name="value">2021-07-08T16:39:17Z</field>
        </element>
      </element>
    3. <element name="issued">
      1. <element name="none">
        <field name="value">2021-05-21</field>
        </element>
      </element>
    4. <element name="updated">
      1. <element name="none">
        <field name="value">2021-06-24T14:11:30Z</field>
        </element>
      </element>
    </element>
  3. <element name="identifier">
    1. <element name="citation">
      1. <element name="es_ES">
        <field name="value">Pharmaceutics 13(6) : (2021) // Article ID 771</field>
        </element>
      </element>
    2. <element name="issn">
      1. <element name="none">
        <field name="value">1999-4923</field>
        </element>
      </element>
    3. <element name="uri">
      1. <element name="none">
        <field name="value">http://hdl.handle.net/10810/52184</field>
        </element>
      </element>
    4. <element name="doi">
      1. <element name="none">
        <field name="value">10.3390/pharmaceutics13060771</field>
        </element>
      </element>
    </element>
  4. <element name="description">
    1. <element name="abstract">
      1. <element name="es_ES">
        <field name="value">Fabry disease (FD) is a monogenic X-linked lysosomal storage disorder caused by a deficiency in the lysosomal enzyme α-Galactosidase A (α-Gal A). It is a good candidate to be treated with gene therapy, in which moderately low levels of enzyme activity should be sufficient for clinical efficacy. In the present work we have evaluated the efficacy of a non-viral vector based on solid lipid nanoparticles (SLN) to increase α-Gal A activity in an FD mouse model after intravenous administration. The SLN-based vector incremented α-Gal A activity to about 10%, 15%, 20% and 14% of the levels of the wild-type in liver, spleen, heart and kidney, respectively. In addition, the SLN-based vector significantly increased α-Gal A activity with respect to the naked pDNA used as a control in plasma, heart and kidney. The administration of a dose per week for three weeks was more effective than a single-dose administration. Administration of the SLN-based vector did not increase liver transaminases, indicative of a lack of toxicity. Additional studies are necessary to optimize the efficacy of the system; however, these results reinforce the potential of lipid-based nanocarriers to treat FD by gene therapy.</field>
        </element>
      </element>
    2. <element name="sponsorship">
      1. <element name="es_ES">
        <field name="value">This research was funded by Merck Salud Foundation, MCIU/AEI/FEDER, UE (RTI2018-098672-B-I00) and by the University of the Basque Country UPV/EHU (GIU17/032).</field>
        </element>
      </element>
    </element>
  5. <element name="language">
    1. <element name="iso">
      1. <element name="es_ES">
        <field name="value">eng</field>
        </element>
      </element>
    </element>
  6. <element name="publisher">
    1. <element name="es_ES">
      1. <field name="value">MDPI</field>
      </element>
    </element>
  7. <element name="relation">
    1. <element name="es_ES">
      1. <field name="value">info:eu-repo/grantAgreement/MCIU/RTI2018-098672-B-I00</field>
      </element>
    2. <element name="publisherversion">
      1. <element name="es_ES">
        <field name="value">https://www.mdpi.com/1999-4923/13/6/771</field>
        </element>
      </element>
    </element>
  8. <element name="rights">
    1. <element name="es_ES">
      1. <field name="value">info:eu-repo/semantics/openAccess</field>
      </element>
    2. <element name="uri">
      1. <element name="none">
        <field name="value">http://creativecommons.org/licenses/by/3.0/es/</field>
        </element>
      </element>
    3. <element name="holder">
      1. <element name="es_ES">
        <field name="value">© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</field>
        </element>
      </element>
    </element>
  9. <element name="subject">
    1. <element name="es_ES">
      1. <field name="value">gene therapy</field>
      2. <field name="value">non-viral vectors</field>
      3. <field name="value">solid lipid nanoparticles</field>
      4. <field name="value">pDNA</field>
      5. <field name="value">Fabry disease</field>
      6. <field name="value">Fabry mice</field>
      7. <field name="value">α-galactosidase A</field>
      8. <field name="value">intravenous administration</field>
      </element>
    </element>
  10. <element name="title">
    1. <element name="es_ES">
      1. <field name="value">α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice</field>
      </element>
    </element>
  11. <element name="type">
    1. <element name="es_ES">
      1. <field name="value">info:eu-repo/semantics/article</field>
      </element>
    </element>
  12. <element name="departamentoes">
    1. <element name="none">
      1. <field name="value">Farmacia y ciencias de los alimentos</field>
      </element>
    </element>
  13. <element name="departamentoeu">
    1. <element name="none">
      1. <field name="value">Farmazia eta elikagaien zientziak</field>
      </element>
    </element>
  </element>
2. <element name="bundles">
  1. <element name="bundle">
    1. <field name="name">TEXT</field>
    2. <element name="bitstreams">
      1. <element name="bitstream">
        <field name="name">pharmaceutics-13-00771-v2.pdf.txt</field>
        <field name="originalName">pharmaceutics-13-00771-v2.pdf.txt</field>
        <field name="description">Extracted text</field>
        <field name="format">text/plain</field>
        <field name="size">56103</field>
        <field name="url">http://addi.ehu.es/bitstream/10810/52184/4/pharmaceutics-13-00771-v2.pdf.txt</field>
        <field name="checksum">69382e02720acd3fe0bcd3b71caa0f86</field>
        <field name="checksumAlgorithm">MD5</field>
        <field name="sid">4</field>
        <field name="drm">open access</field>
        </element>
      </element>
    </element>
  2. <element name="bundle">
    1. <field name="name">ORIGINAL</field>
    2. <element name="bitstreams">
      1. <element name="bitstream">
        <field name="name">pharmaceutics-13-00771-v2.pdf</field>
        <field name="format">application/pdf</field>
        <field name="size">1420923</field>
        <field name="url">http://addi.ehu.es/bitstream/10810/52184/1/pharmaceutics-13-00771-v2.pdf</field>
        <field name="checksum">a559d129762e0e9db8f71dd05212f44a</field>
        <field name="checksumAlgorithm">MD5</field>
        <field name="sid">1</field>
        <field name="drm">open access</field>
        </element>
      </element>
    </element>
  3. <element name="bundle">
    1. <field name="name">LICENSE</field>
    2. <element name="bitstreams">
      1. <element name="bitstream">
        <field name="name">license.txt</field>
        <field name="originalName">license.txt</field>
        <field name="format">text/plain; charset=utf-8</field>
        <field name="size">3890</field>
        <field name="url">http://addi.ehu.es/bitstream/10810/52184/2/license.txt</field>
        <field name="checksum">c3850b7ad7d2a73adecc8b1227483e96</field>
        <field name="checksumAlgorithm">MD5</field>
        <field name="sid">2</field>
        <field name="drm">open access</field>
        </element>
      </element>
    </element>
  4. <element name="bundle">
    1. <field name="name">SWORD</field>
    2. <element name="bitstreams">
      1. <element name="bitstream">
        <field name="name">packager-60d49291.zip</field>
        <field name="description">SWORD deposit package</field>
        <field name="format">application/octet-stream</field>
        <field name="size">1332365</field>
        <field name="url">http://addi.ehu.es/bitstream/10810/52184/3/packager-60d49291.zip</field>
        <field name="checksum">df7affe06c448a48af33c665bf1477fc</field>
        <field name="checksumAlgorithm">MD5</field>
        <field name="sid">3</field>
        <field name="drm">open access</field>
        </element>
      </element>
    </element>
  </element>
3. <element name="others">
  1. <field name="handle">10810/52184</field>
  2. <field name="identifier">oai:addi.ehu.eus:10810/52184</field>
  3. <field name="lastModifyDate">2022-12-19 20:08:14.0</field>
  4. <field name="drm">open access</field>
  </element>
4. <element name="repository">
  1. <field name="name">ADDI</field>
  2. <field name="mail">addi@ehu.eus</field>
  </element>
5. <element name="license">
  1. <field name="bin">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</field>
  </element>
</metadata>