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pubmed-article:19727131pubmed:abstractTextEngineered 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.lld:pubmed
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pubmed-article:19727131pubmed:volume16lld:pubmed
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pubmed-article:19727131pubmed:pagination1292-9lld:pubmed
pubmed-article:19727131pubmed:dateRevised2011-11-17lld:pubmed
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pubmed-article:19727131pubmed:year2009lld:pubmed
pubmed-article:19727131pubmed:articleTitleNeuroprotection using gene therapy to induce vascular endothelial growth factor-A expression.lld:pubmed
pubmed-article:19727131pubmed:affiliationDepartment of Neurology, University of Michigan Medical Center, Ann Arbor, MI, USA.lld:pubmed
pubmed-article:19727131pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:19727131pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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pubmed-article:19727131pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed