In vivo selection yields AAV-B1 capsid for central nervous system and muscle gene therapy

Sourav R. Choudhury, Zachary Fitzpatrick, Anne F. Harris, Stacy A. Maitland, Jennifer S. Ferreira, Yuanfan Zhang, Shan Ma, Rohit B. Sharma, Heather L. Gray-Edwards, Jacob A. Johnson, Aime K. Johnson, Laura C. Alonso, Claudio Punzo, Kathryn R. Wagner, Casey A. Maguire, Robert M. Kotin, Douglas R. Martin, Miguel Sena-Esteves

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1247-1257
Number of pages11
JournalMolecular Therapy
Issue number7
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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