Biodistribution Analysis of Adeno-Associated Viral Vectors of Serotypes 9 and rh.10 Encoding Arylsulfatase A Following Prior Immunization with Serotype 9 in Pigs
https://doi.org/10.26907/2542-064X.2024.4.683-703
Abstract
Lysosomal storage diseases are a group of inherited disorders caused by lysosomal dysfunction, impairing cellular metabolic enzymes, signaling pathways, and other biological processes. Among them is metachromatic leukodystrophy (MLD) associated with arylsulfatase A (ARSA) deficiency, which leads to the accumulation of sulfatides and the destruction of myelin sheaths in the nervous system. This study evaluates the therapeutic efficacy of adeno-associated viruses (AAVs) in treating neurodegenerative diseases such as MLD. The biodistribution and safety of AAV9-ARSA and AAVrh.10-ARSA vectors following prior immunization in pigs were shown. The immune aspects of AAV-based gene therapy were outlined. Its potential efficacy and durability limitations were discussed.
Supporting agencies: This study was funded by the subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientific activities (project no. FZSM-2023-0011) and supported by the Kazan Federal University Strategic Academic Leadership Program.
About the Authors
A. I. Mullagulova
Kazan Federal University
Russian Federation
Russian Federation
Kazan, 420008
A. A. Shaimardanova
Kazan Federal University
Russian Federation
Russian Federation
Kazan, 420008
Ya. O. Mukhamedshina
Kazan Federal University; Republican Clinical Hospital of Tatarstan
Russian Federation
Russian Federation
Kazan, 420008
Kazan, 420064
V. V. Solovyeva
Kazan Federal University
Russian Federation
Russian Federation
Kazan, 420008
A. Ibrahim
Kazan Federal University
Russian Federation
Russian Federation
Kazan, 420008
A. A. Rizvanov
Kazan Federal University; Tatarstan Academy of Sciences
Russian Federation
Russian Federation
Kazan, 420008
Kazan, 420111
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For citations:
Mullagulova A.I., Shaimardanova A.A., Mukhamedshina Ya.O., Solovyeva V.V., Ibrahim A., Rizvanov A.A. Biodistribution Analysis of Adeno-Associated Viral Vectors of Serotypes 9 and rh.10 Encoding Arylsulfatase A Following Prior Immunization with Serotype 9 in Pigs. Uchenye Zapiski Kazanskogo Universiteta Seriya Estestvennye Nauki. 2024;166(4):683–703. (In Russ.) https://doi.org/10.26907/2542-064X.2024.4.683-703
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