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Mol Ther. 2016 Aug;24(7):1247-57. doi: 10.1038/mt.2016.84. Epub 2016 Apr 27.

In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy.

Author information

1
Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
2
Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
3
Department of Neurology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
4
The Hugo W. Moser Research Institute, Kennedy Krieger Institute and Departments of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
5
Department of Ophthalmology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
6
Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
7
Scott-Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
8
Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
9
Voyager Therapeutics, Cambridge, Massachusetts, USA.
10
Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.

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.

PMID:
27117222
PMCID:
PMC5088762
DOI:
10.1038/mt.2016.84
[Indexed for MEDLINE]
Free PMC Article

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