SCREENING CATIONIC LIPIDS FOR GENE DELIVERY ACTIVITY

描述：（改编自申请人摘要）。为了充分利用合成的非病毒基因递送系统提供的临床基因治疗机会，需要改进它们的功效，并且鉴定改进的合成载体的一种方法是在定量的功效指示测定中筛选大量候选物。一个高通量的测定，使2000转染条件进行定量筛选，每周是可用的。从由144种纯阳离子两亲物组成的化合物库中，随机选择13种化合物，发现2种化合物的基因递送效力超过最有效的市售阳离子脂质试剂。因此，该文库可以包含具有相等或甚至更大效力的更多化合物。这笔资金将用于合成10克迄今为止发现的最具活性的化合物，并筛选库中其余的脂质。从这个定量调查的数据库将被用来开发结构活性关系，以指导更有效的阳离子脂质类似物的合成，并确定更多的商业化的候选人。拟定商业应用：从该筛选活动中鉴定的阳离子脂质制剂将作为科学家的转染试剂商业化。最终，这些制剂中的一些可能成为商业化的人类药物基因治疗产品。

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.