Evaluation of nonviral gene editing systems in the brain assisted by focused ultrasound

聚焦超声辅助下大脑非病毒基因编辑系统的评估

基本信息

批准号：
10658371
负责人：
KAM W LEONG
金额：
$ 32.17万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2023-07-31
项目状态：
已结题

项目摘要

Supplemental Proposal Evaluation of nonviral gene editing systems in the brain assisted by focused ultrasound Abstract Efficient nonviral gene editing of the brain may help tackle some of the intractable neuronal degenerative disorders. Compared with viral gene editing, it is more translatable since it should have more manageable toxicity and immunogenicity. Many gene editing applications may require multiple administrations if there is a high turnover of the tissue. Viral gene editing systems would be unsuitable because of concerns of immunogenicity. The major barrier to nonviral gene editing of the brain is the BBB. We previously pioneered the use of focused ultrasound (FUS) technology to achieve noninvasive, brain-specific delivery of therapeutic payloads including small molecules, proteins and adeno-associated virus (AAV). This Supplemental proposal aims to compare the nonviral gene editing systems developed by other SCGE teams. It is expected that these nonviral gene editing systems have shown promising editing efficiency in tissues other than the brain. The FUS delivery will be performed at Columbia on Ai9 mice and the brain tissues sent to JAX for independent gene editing analysis. The final experimental design will be established in consultation with the PIs. This unbiased comparative study will define the possibilities and limitations of nonviral brain gene editing in the brain assisted by FUS.

补充建议对聚焦超声协助的大脑中非病毒基因编辑系统的评估抽象的大脑的有效非病毒基因编辑可能有助于解决一些棘手的神经元退行性疾病。与病毒基因编辑相比，它更可转换，因为它应该具有更易于管理的毒性和免疫原性。如果有一个基因编辑应用程序，则可能需要多个管理组织的更高周转率。病毒基因编辑系统将不适合免疫原性。大脑非病毒基因编辑的主要障碍是BBB。我们以前开创了先驱使用重点超声（FUS）技术来实现无创，大脑特异性的治疗性交付有效载荷包括小分子，蛋白质和腺相关病毒（AAV）。这项补充建议旨在比较其他SCGE团队开发的非病毒基因编辑系统。预计这些非病毒基因编辑系统已显示出有希望的编辑效率在大脑以外的其他组织中。 FUS 分娩将在哥伦比亚对AI9小鼠进行，并发送到JAX的脑组织以进行独立基因编辑分析。最终的实验设计将在与PIS协商时建立。这个公正比较研究将定义大脑中非病毒脑基因编辑的可能性和局限性由FUS。