In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy
Department of Neurology; Gene Therapy Center; Department of Ophthalmology; Diabetes Center of Excellence; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular and Cellular Neuroscience | Molecular Biology | Neuroscience and Neurobiology | Therapeutics
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, beta-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 of Published Version
Mol Ther. 2016 Aug;24(7):1247-57. doi: 10.1038/mt.2016.84. Epub 2016 Apr 27. Link to article on publisher's site
Molecular therapy : the journal of the American Society of Gene Therapy
Choudhury, Sourav Roy; Harris, Anne F.; Maitland, Stacy A.; Ferreira, Jennifer; Ma, Shan; Sharma, Rohit B.; Alonso, Laura C.; Punzo, Claudio; Kotin, Robert M.; and Sena-Esteves, Miguel, "In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy" (2016). UMass Metabolic Network Publications. 37.