Efficient Retrograde Neuronal Transduction Utilizing Self-complementary AAV1.

Efficient Retrograde Neuronal Transduction Utilizing Self-complementary AAV1. Research Abstract Details 

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Efficient Retrograde Neuronal Transduction Utilizing Self-complementary AAV1. Abstract Text:

Edmund R Hollis Ii,Ken Kadoya,Matthew Hirsch,Richard J Samulski,Mark H Tuszynski,

Adeno-associated virus (AAV) is frequently used for gene transfer into the central nervous system (CNS). Similar to adenovirus and rabies virus, AAV can be taken up by axons and retrogradely transported, resulting in neuronal gene expression distant from the injection site. We investigated the retrograde transport properties of self-complementary AAV (scAAV) serotypes 1-6 following peripheral injection. Injection of scAAV into either rat extensor carpi muscle or sciatic nerve resulted in detectable retrograde vector transport and reporter gene expression in spinal cord motor neurons (MNs). Serotype 1 resulted in the highest level of retrograde transport, with 4.1 +/- 0.3% of cervical MNs projecting to the extensor carpi transduced following intramuscular injection, and 7.5 +/- 3.1% of lumbar MNs transduced after sciatic nerve injection. In contrast to scAAV1, retrograde transduction with scAAV2 was undetectable following intramuscular injection, and was detected in only 0.81 +/- 0.15% of MNs projecting to the sciatic nerve following intranerve injection. Furthermore, sciatic injection of single-stranded AAV1 required injection of tenfold higher numbers of viral particles for detectable transgene expression compared to scAAV1, and then only 0.91 +/- 0.24% of lumbar MNs were transduced. Our data provide the basis for increased retrograde transduction efficiency using peripheral injections of scAAV1 vectors for therapeutic gene delivery to the spinal cord.Molecular Therapy (2007); 16 2, 296-301. doi:10.1038/sj.mt.6300367.

Efficient Retrograde Neuronal Transduction Utilizing Self-complementary AAV1. Publishing Authors By Initials

ER Hollis Ii,K Kadoya,M Hirsch,RJ Samulski,MH Tuszynski,

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Efficient Retrograde Neuronal Transduction Utilizing Self-complementary AAV1. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Molecular therapy : the journal of the American So

VOLUME: 16

Page Numbers: 296-301

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0016

DAY: 27

MONTH: 11

YEAR: 2007

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LANGUAGE: eng

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AFFILIATION: 1Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.

Country: United States

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MEDLINETA: Mol Ther

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