Source:http://linkedlifedata.com/resource/pubmed/id/19727131
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2009-11-12
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pubmed:abstractText |
Engineered zinc-finger protein (ZFP) transcription factors induce the expression of endogenous genes and can be remotely delivered using adenoviral vectors. One such factor, Ad-32Ep65-Flag (Ad-p65), targets and induces expression of vascular endothelial growth factor (VEGF; also called VEGF-A) splice variants in their normal biological stoichiometry. We show that Ad-p65 transfection of primary motor neurons results in VEGF variant expression and a significant increase in axon outgrowth in these cells. Given the neuroprotective effects of VEGF and its ability to increase neurite outgrowth, we examined the efficacy of Ad-p65 to enhance motor neuron regeneration in vivo using rats that have undergone recurrent laryngeal nerve (RLN)-crush injury. Injection of Ad-p65 after RLN crush accelerated the return of vocal fold mobility and the percentage of nerve-endplate contacts in the thyroarytenoid muscle. Overall, adenoviral delivery of an engineered ZFP transcription factor inducing VEGF-A splice variant expression enhances nerve regeneration. ZFP transcription factor gene therapy to increase expression of the full complement of VEGF-A splice variants is a promising avenue for the treatment of nerve injury and neurodegeneration.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1476-5462
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1292-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19727131-Adenoviridae,
pubmed-meshheading:19727131-Animals,
pubmed-meshheading:19727131-Gene Therapy,
pubmed-meshheading:19727131-Genetic Vectors,
pubmed-meshheading:19727131-Motor Endplate,
pubmed-meshheading:19727131-Motor Neurons,
pubmed-meshheading:19727131-Nerve Crush,
pubmed-meshheading:19727131-Nerve Regeneration,
pubmed-meshheading:19727131-Rats,
pubmed-meshheading:19727131-Rats, Sprague-Dawley,
pubmed-meshheading:19727131-Recurrent Laryngeal Nerve Injuries,
pubmed-meshheading:19727131-Transfection,
pubmed-meshheading:19727131-Up-Regulation,
pubmed-meshheading:19727131-Vascular Endothelial Growth Factor A,
pubmed-meshheading:19727131-Vocal Cord Paralysis,
pubmed-meshheading:19727131-Vocal Cords,
pubmed-meshheading:19727131-Zinc Fingers
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pubmed:year |
2009
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pubmed:articleTitle |
Neuroprotection using gene therapy to induce vascular endothelial growth factor-A expression.
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pubmed:affiliation |
Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Evaluation Studies,
Research Support, N.I.H., Extramural
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