Neuroprotection using gene therapy to induce vascular endothelial growth factor-A expression
| Autor: | S K Spratt, Sang Su Oh, Stacey A. Sakowski, Eva L. Feldman, J S Lunn, Norman D. Hogikyan, S B Heavener, Kevin Fung |
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| Rok vydání: | 2009 |
| Předmět: |
Vascular Endothelial Growth Factor A
Neurite Nerve Crush Genetic Vectors Vocal Cords Biology Transfection Neuroprotection Motor Endplate Article Adenoviridae Rats Sprague-Dawley chemistry.chemical_compound Genetics medicine Animals Molecular Biology Transcription factor Motor Neurons Zinc Fingers Anatomy Genetic Therapy Nerve injury Cell biology Nerve Regeneration Rats Up-Regulation Vascular endothelial growth factor Vascular endothelial growth factor A chemistry Recurrent Laryngeal Nerve Injuries Molecular Medicine medicine.symptom Transcription Factor Gene Vocal Cord Paralysis |
| Zdroj: | Gene therapy. 16(11) |
| ISSN: | 1476-5462 |
| Popis: | Engineered zinc-finger protein transcription factors induce the expression of endogenous genes and can be remotely delivered using adenoviral vectors. One such factor, Ad-32Ep65-Flag, targets and induces expression of vascular endothelial growth factor splice variants in their normal biological stoichiometry. We demonstrate that Ad-32Ep65-Flag transfection of primary motor neurons results in vascular endothelial growth factor variant expression and a significant increase in axon outgrowth in these cells. Given the neuroprotective effects of vascular endothelial growth factor and its ability to increase neurite outgrowth, we examined the efficacy of Ad-32Ep65-Flag to enhance motor neuron regeneration in vivo using rats that have undergone recurrent laryngeal nerve crush injury. Injection of Ad-32Ep65-Flag following recurrent laryngeal nerve 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 zinc-finger protein transcription factor inducing vascular endothelial growth factor splice variant expression enhances nerve regeneration. Zinc-finger protein transcription factor gene therapy to increase expression of the full complement of vascular endothelial growth factor splice variants is a promising avenue for the treatment of nerve injury and neurodegeneration. |
| Databáze: | OpenAIRE |
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