| Autor: |
Piotr Hadaczek, Lisa Stanek, Agnieszka Ciesielska, Vivek Sudhakar, Lluis Samaranch, Philip Pivirotto, John Bringas, Catherine O'Riordan, Bryan Mastis, Waldy San Sebastian, John Forsayeth, Seng H Cheng, Krystof S Bankiewicz, Lamya S Shihabuddin |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Molecular Therapy: Methods & Clinical Development, Vol 3, Iss C (2016) |
| Druh dokumentu: |
article |
| ISSN: |
2329-0501 |
| DOI: |
10.1038/mtm.2016.37 |
| Popis: |
Huntington's disease (HD) is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt) protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV), AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP), with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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