BIODEGRADABLE PROTON SPONGES FOR GENE THERAPY

提出的研究的主要目标是发展可生物降解的聚合转染载体，可应用于人类基因治疗相关的问题。提案的前半部分详细介绍了一种合成和表征新型含胺超支化聚酯的实验方法。这些材料被设计成阳离子“质子海绵”材料的可生物降解类似物。这些“质子海绵”目前的形式是不可生物降解的，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络合谱所需的具体方法，以及将用于确定其作为质粒DNA体外转移载体的有效性的测定。所提出的材料代表了现有聚合物基载体的重大进步。这些新材料的生物可降解性可能导致无毒高效聚合物载体的发展，最终可用于体内遗传疾病的治疗。

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.