Title | In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Choudhury SR, Fitzpatrick Z, Harris AF, Maitland SA, Ferreira JS, Zhang Y, Ma S, Sharma RB, Gray-Edwards HL, Johnson JA, Johnson AK, Alonso LC, Punzo C, Wagner KR, Maguire CA, Kotin RM, Martin DR, Sena-Esteves M |
Journal | Mol Ther |
Volume | 24 |
Issue | 7 |
Pagination | 1247-57 |
Date Published | 2016 08 |
ISSN | 1525-0024 |
Keywords | Animals, Capsid Proteins, Central Nervous System, Dependovirus, Gene Expression, Gene Transfer Techniques, Genes, Reporter, Genetic Therapy, Genetic Vectors, Humans, Mice, Models, Molecular, Muscles, Protein Conformation, Transduction, Genetic, Transgenes, Viral Tropism |
Abstract | Adeno-associated viral (AAV) vectors have shown promise as a platform for gene therapy of neurological disorders. Achieving global gene delivery to the central nervous system (CNS) is key for development of effective therapies for many of these diseases. Here we report the isolation of a novel CNS tropic AAV capsid, AAV-B1, after a single round of in vivo selection from an AAV capsid library. Systemic injection of AAV-B1 vector in adult mice and cat resulted in widespread gene transfer throughout the CNS with transduction of multiple neuronal subpopulations. In addition, AAV-B1 transduces muscle, β-cells, pulmonary alveoli, and retinal vasculature at high efficiency. This vector is more efficient than AAV9 for gene delivery to mouse brain, spinal cord, muscle, pancreas, and lung. Together with reduced sensitivity to neutralization by antibodies in pooled human sera, the broad transduction profile of AAV-B1 represents an important improvement over AAV9 for CNS gene therapy. |
DOI | 10.1038/mt.2016.84 |
Alternate Journal | Mol. Ther. |
PubMed ID | 27117222 |
PubMed Central ID | PMC5088762 |
Grant List | R01 DK095140 / DK / NIDDK NIH HHS / United States R01 NS066310 / NS / NINDS NIH HHS / United States U54 HD060848 / HD / NICHD NIH HHS / United States U54 HD079123 / HD / NICHD NIH HHS / United States |