In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy
Autor: | Kathryn R. Wagner, Aime K. Johnson, Jacob A. Johnson, Rohit Sharma, Zachary Fitzpatrick, Claudio Punzo, Shan Ma, Anne F Harris, Robert M. Kotin, Yuanfan Zhang, Heather L. Gray-Edwards, Laura C. Alonso, Miguel Sena-Esteves, Stacy Maitland, Casey A. Maguire, Sourav Roy Choudhury, Jennifer S Ferreira, Douglas R. Martin |
---|---|
Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Central Nervous System Models Molecular Protein Conformation Genetic enhancement Transgene viruses Central nervous system Genetic Vectors Gene Expression Gene delivery Biology 03 medical and health sciences Transduction (genetics) Mice Genes Reporter Transduction Genetic Drug Discovery Gene expression Genetics medicine Animals Humans Transgenes Molecular Biology Pharmacology Muscles Gene Transfer Techniques Genetic Therapy Dependovirus Virology 3. Good health Cell biology Viral Tropism 030104 developmental biology medicine.anatomical_structure Capsid Tissue tropism Molecular Medicine Capsid Proteins Original Article |
Zdroj: | Molecular therapy : the journal of the American Society of Gene Therapy. 24(7) |
ISSN: | 1525-0024 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |