BIODEGRADABLE PROTON SPONGES FOR GENE THERAPY

该研究的主要目标是开发可生物降解的聚合物转染载体，其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的含胺超支化聚酯的合成和表征的实验方法。这些材料已被设计为充当阳离子“质子海绵”材料的生物可降解类似物。这些“质子海绵”，在其目前的形式，是不可生物降解的，但表现出令人印象深刻的效率作为非病毒基因转移载体。所提出的类似物将在细胞内遇到的条件下降解为无毒产物。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络合特征所需的具体方法，以及用于确定其作为质粒DNA体外转移载体的功效的试验。所提出的材料代表了现有基于聚合物的载体的重大进展。这些新材料的生物降解性可能导致无毒高效的聚合物载体的发展，最终可用于治疗体内遗传性疾病。

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.