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C3 transferase Gene Therapy for CNS Axon Regeneration

C3 transferase Gene Therapy for CNS Axon Regeneration
用于中枢神经系统轴突再生的 C3 转移酶基因治疗
批准号:
8873702
负责人:
ROBERT E GROSS
金额:
$7.8万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-03-01 至 2017-02-28

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中文摘要
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英文摘要
 DESCRIPTION: Pathways in the adult central nervous system (CNS) are unable to regenerate after injury, leaving victims of traumatic nerve damage or degenerative disease severely disabled. Improving the regenerative capacity of the CNS may improve functional recovery, quality of life, as well as decrease overall healthcare costs for many of these patients. A major hurdle, however, is the non-permissive nature of the CNS to axon regeneration. Elucidation of the molecular signaling cascades that inhibits axon re- growth has identified the pivotal role of a common intracellular 'molecular switch' - RhoA GTPase. C3 transferase, a bacterial exoenzyme, inhibits RhoA via ADP- ribosylation and its local application promotes axon re-growth in various CNS injury models. This method of delivery is however limited to a duration of several days, likely insufficient for the regeneration of long axons and sustained neuron survival. To address these issues, we have engineered viral vectors to allow continuous delivery of C3 via gene therapy. A cell-permeable and secretable version of C3 has been developed for more widespread and effective RhoA inactivation. Our objective is to test a variety of different approaches of viral vector - mediated C3 expression to identify the most effective delivery and therapeutic window for CNS axon regeneration in a model of optic nerve injury, the optic nerve crush (ONC). The successful results of these experiments will lay the foundation for the extension of our approach to treat other neuropathology's including spinal cord injury, brain injury, and stroke and neurodegenerative diseases.
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海外基金