Comparison of adeno-associated viral vector serotypes for spinal cord and motor neuron gene delivery

Brooke R. Snyder; Steven J. Gray; Eric T. Quach; Jeremiah W. Huang; Cary H. Leung; R. Jude Samulski; Nicholas M. Boulis; Thais Federici

doi:10.1089/hum.2011.008

Comparison of adeno-associated viral vector serotypes for spinal cord and motor neuron gene delivery

Brooke R. Snyder, Steven J. Gray, Eric T. Quach, Jeremiah W. Huang, Cary H. Leung, R. Jude Samulski, Nicholas M. Boulis, Thais Federici

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

126 Scopus citations

Abstract

Gene therapy for motor neuron diseases requires efficient gene delivery to motor neurons (MNs) throughout the spinal cord and brainstem. The present study compared adeno-associated viral (AAV) vector serotypes 1, 6, 8, and 9 for spinal cord delivery in adult mice, by the intraparenchymal or intrathecal route of administration. Whereas intraparenchymal injections resulted in local transduction of the lumbar segment of the spinal cord, intrathecal injections led to a broader distribution, transducing cells along the sacral, lumbar, and lower thoracic spinal cord. Overall, AAV6 and AAV9 performed better than the other serotypes. Dramatic differences in cell-specific expression patterns could be observed when constructs bearing the chicken β-actin (Cba) versus cytomegalovirus (CMV) promoter were compared. In summary, intrathecal delivery of AAV6 or AAV9 vectors containing the CMV promoter yielded the strongest levels of biodistribution and MN transduction in the spinal cord.

Original language	English (US)
Pages (from-to)	1129-1135
Number of pages	7
Journal	Human Gene Therapy
Volume	22
Issue number	9
DOIs	https://doi.org/10.1089/hum.2011.008
State	Published - Sep 1 2011

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics

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abstract = "Gene therapy for motor neuron diseases requires efficient gene delivery to motor neurons (MNs) throughout the spinal cord and brainstem. The present study compared adeno-associated viral (AAV) vector serotypes 1, 6, 8, and 9 for spinal cord delivery in adult mice, by the intraparenchymal or intrathecal route of administration. Whereas intraparenchymal injections resulted in local transduction of the lumbar segment of the spinal cord, intrathecal injections led to a broader distribution, transducing cells along the sacral, lumbar, and lower thoracic spinal cord. Overall, AAV6 and AAV9 performed better than the other serotypes. Dramatic differences in cell-specific expression patterns could be observed when constructs bearing the chicken β-actin (Cba) versus cytomegalovirus (CMV) promoter were compared. In summary, intrathecal delivery of AAV6 or AAV9 vectors containing the CMV promoter yielded the strongest levels of biodistribution and MN transduction in the spinal cord.",

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AU - Leung, Cary H.

AU - Samulski, R. Jude

AU - Boulis, Nicholas M.

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Comparison of adeno-associated viral vector serotypes for spinal cord and motor neuron gene delivery

Abstract

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