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

doi:10.1038/mt.2016.84

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

Kennedy Krieger Institute

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1247-1257
Number of pages	11
Journal	Molecular Therapy
Volume	24
Issue number	7
DOIs	https://doi.org/10.1038/mt.2016.84
State	Published - Aug 1 2016

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

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Choudhury, S. R., Fitzpatrick, Z., Harris, A. F., Maitland, S. A., Ferreira, J. S., Zhang, Y., Ma, S., Sharma, R. B., Gray-Edwards, H. L., Johnson, J. A., Johnson, A. K., Alonso, L. C., Punzo, C., Wagner, K. R., Maguire, C. A., Kotin, R. M., Martin, D. R., & Sena-Esteves, M. (2016). In vivo selection yields AAV-B1 capsid for central nervous system and muscle gene therapy. Molecular Therapy, 24(7), 1247-1257. https://doi.org/10.1038/mt.2016.84

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 2016, 'In vivo selection yields AAV-B1 capsid for central nervous system and muscle gene therapy', Molecular Therapy, vol. 24, no. 7, pp. 1247-1257. https://doi.org/10.1038/mt.2016.84

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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.",

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

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

Abstract

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