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.

补充提案聚焦超声辅助下大脑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失调。与病毒基因编辑相比，它更具可翻译性，因为它应该更易于管理毒性和免疫原性。如果存在以下情况，许多基因编辑应用程序可能需要多次管理：组织的高周转率。由于担心病毒基因编辑系统不适合免疫原性。大脑非病毒基因编辑的主要障碍是血脑屏障。我们之前就开创了使用聚焦超声 (FUS) 技术实现无创、针对大脑的治疗递送有效负载包括小分子、蛋白质和腺相关病毒（AAV）。本补充提案旨在比较其他 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在大脑以外的组织中显示出有希望的编辑效率。福斯 Ai9小鼠将在哥伦比亚进行交付，脑组织将被送往JAX获取独立基因编辑分析。最终的实验设计将与 PI 协商确定。这个不偏不倚比较研究将确定非病毒脑基因编辑在脑辅助中的可能性和局限性由FUS。