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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

Procedència

Fitxa

Títol:: 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
Descripció:: 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
Relació:: 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
Editor:: MDPI
Drets:: 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
Format:: application/pdf

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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>
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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>
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32. <rights>info:eu-repo/semantics/openAccess</rights>
33. <publisher>MDPI</publisher>
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9. <dc:subject>gene therapy</dc:subject>
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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>
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