SCREENING CATIONIC LIPIDS FOR GENE DELIVERY ACTIVITY

筛选阳离子脂质的基因传递活性

• 批准号: 2867974
• 负责人: PHILIP Louis FELGNER
• 金额: $ 10.44万
• 依托单位: GENE THERAPY SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2867974
• 关键词: gene targeting; gene therapy; genetic library; liposomes; technology /technique development; transfection /expression vector

DESCRIPTION: (adapted from applicant's abstract) ). In order to take full advantage of the clinical gene therapy opportunities offered by synthetic nonviral gene delivery systems, their efficacy needs to be improved, and one way to identify improved synthetic vectors is to screen a large number of candidates in a quantitative, efficacy indicating assay. A high throughput assay which enables 2000 transfection conditions to be quantitatively screened per week is available. From a compound library consisting of 144 pure cationic amphiphiles, 13 compounds were selected at random and 2 compounds were found with gene delivery potency exceeding that of the most potent commercially available cationic lipid reagents. Hence, this library may contain more compounds with equal or even greater potency. The grant will be used to synthesize 10 grams of the most active compound identified so far, and to screen the rest of the lipids in the library. The database from this quantitative survey will be used to develop structure activity relationships to guide the synthesis of more potent cationic lipid analogs and to identify more candidates for commercialization. PROPOSED COMMERCIAL APPLICATION: The cationic lipid formulations identified from this screening activity will be commercialized as tranfection reagents for scientists. Ultimately some of these formulation may become commercialized as human pharmaceutical gene therapy products.

描述：(改编自申请人的摘要)。为了充分利用合成非病毒基因传递系统提供的临床基因治疗机会，它们的有效性需要提高，而鉴定改进的合成载体的方法之一是在定量的、疗效指示的试验中筛选大量候选基因。一种能够每周定量筛选2000种转染性条件的高通量分析方法是可用的。从144个纯阳离子两亲化合物文库中，随机选择了13个化合物，其中2个化合物的基因传递能力超过了市面上最有效的阳离子脂类试剂。因此，这个文库可能包含更多具有同等甚至更高效力的化合物。这笔赠款将用于合成10克迄今已确定的最有活性的化合物，并用于筛选图书馆中的其余类脂。这个定量调查的数据库将被用来发展结构活性关系，指导合成更有效的阳离子脂类似物，并确定更多的商业化候选者。建议的商业应用：从这次筛选活动中确定的阳离子脂类制剂将作为科学家的转基因试剂进行商业化。最终，这些制剂中的一些可能会作为人类药物基因治疗产品商业化。