Novel Properties of Tyrosine-mutant AAV2 Vectors in the Mouse Retina
| Autor: | Seok-Hong Min, Alfred S. Lewin, Li Zhong, Antonette Bennett, Hilda Petrs-Silva, William W. Hauswirth, Giridhara R. Jayandharan, Mavis Agbandje-McKenna, Jijing Pang, Andy W. Neeley, Arun Srivastava, Astra Dinculescu, Qiuhong Li, Wen-Tao Deng, Lakshmanan Govindasamy, Baozheng Li, Vince A. Chiodo |
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| Rok vydání: | 2011 |
| Předmět: |
viruses
Transgene Genetic Vectors Mutant Biology Retina Virus Mice Transduction (genetics) Drug Discovery medicine Genetics Animals Point Mutation Tyrosine Molecular Biology Pharmacology Point mutation Dependovirus Molecular biology Mice Inbred C57BL medicine.anatomical_structure Capsid Mutation Mutagenesis Site-Directed Molecular Medicine Original Article |
| Zdroj: | Molecular Therapy. 19(2):293-301 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2010.234 |
| Popis: | Vectors based on adeno-associated virus serotype 2 (AAV2) have been used extensively in many gene-delivery applications, including several successful clinical trials for one type of Leber congenital amaurosis in the retina. Many studies have focused on improving AAV2 transduction efficiency and cellular specificity by genetically engineering its capsid. We have previously shown that vectors-containing single-point mutations of capsid surface tyrosines in serotypes AAV2, AAV8, and AAV9 displayed significantly increased transduction efficiency in the retina compared with their wild-type counterparts. In the present study, we evaluated the transduction characteristics of AAV2 vectors containing combinations of multiple tyrosine to phenylalanine mutations in seven highly conserved surface-exposed capsid tyrosine residues following subretinal or intravitreal delivery in adult mice. The multiply mutated vectors exhibited different in vivo transduction properties, with some having a unique ability of transgene expression in all retinal layers. Such novel vectors may be useful in developing valuable new therapeutic strategies for the treatment of many genetic diseases. |
| Databáze: | OpenAIRE |
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