BIODEGRADABLE PROTON SPONGES FOR GENE THERAPY

用于基因治疗的可生物降解质子海绵

• 批准号: 6014592
• 负责人: DAVID M LYNN
• 金额: $ 3.03万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6014592
• 关键词: acidity /alkalinity; analog; biomaterial compatibility; biomaterial development /preparation; chemical property; cytotoxicity; gene therapy; hydropathy; physical property; plasmids; polymers; transfection /expression vector

The primary goal of the proposed research is the development of biodegradable polymeric transfection vectors which can be applied to problems associated with human gene therapy. The first half of the proposal details an experimental approach to the synthesis and characterization of new aminc-containing hyperbranched polyesters. These materials have been designed to act as biodegradable analogs of cationic "proton sponge" materials. These "proton sponges," in their current forms, are not biodegradable but demonstrate impressive efficiencies as non-viral gene transfer vectors. The proposed analogs will degrade to non-toxic products under conditions encountered within the cell. The second half of the proposal outlines the specific approaches necessary to determine the biocompatibilities, biodegradabilities, and DNA-complexation profiles of these materials as well as the assays that will be used to determine their efficacies as vectors for the in vitro transfer of plasmid DNA. The proposed materials represent significant advances over existing polymer-based vectors. The biodegradabilities of these new materials may lead to the development of non-toxic highly-efficient polymeric vectors which could eventually be used for the treatment of genetic diseases in vivo.

拟议研究的主要目标是开发可生物降解的聚合转染载体，可应用于与人类基因治疗相关的问题。该提案的前半部分详细介绍了新型含胺超支化聚酯的合成和表征的实验方法。这些材料被设计用作阳离子“质子海绵”材料的可生物降解类似物。这些“质子海绵”目前的形式不可生物降解，但作为非病毒基因转移载体表现出令人印象深刻的效率。所提出的类似物在细胞内遇到的条件下将降解为无毒产物。该提案的后半部分概述了确定这些材料的生物相容性、生物降解性和 DNA 复合特征所需的具体方法，以及用于确定其作为质粒 DNA 体外转移载体功效的测定方法。所提出的材料代表了现有基于聚合物的载体的显着进步。这些新材料的生物降解性可能会导致无毒高效聚合物载体的开发，最终可用于治疗体内遗传疾病。