NOVEL LIPOSOMES FOR GENE THERAPY

阳离子脂质转染已成为选择的方法， 在体外将基因传递给大多数细胞类型。 目前这一代 的阳离子脂质转染试剂在体外是有效的， 它们通过静电作用与DNA形成稳定的二元复合物 交互. 形成后，这些复合物携带净正电荷。 促进它们与净负电荷相互作用的电荷 细胞的质膜。 缺乏体内可转染性 由于缺乏转染活性的分布， 复合物，因为带正电荷的 复合物和带负电荷的细胞外基质组分。 第一阶段的具体目标包括：1.合成和物理 各种新型阳离子两亲分子的表征。2. 使用标准细胞系表征体外可转染性， 组织培养3.相关的物理性质和转染 与内体功能和状态的能力。4.使用特定配体， 用于测定配体依赖性的指定阳离子脂质体制剂 组织培养中的转染。 建议的商业应用 这种非病毒基因递送的新方法将通过以下方式商业化： 1)将该技术以试剂盒的形式出售给生物医学和 基础研究人员2）授权体内基因递送技术 用于治疗遗传疾病的制药公司， 获得性疾病3）许可体内基因递送技术 给制药公司用于疫苗研发

Cationic lipid transfection has become the method of choice for delivering genes to most cell types in vitro. The current generation of cationic lipid transfection reagents are effective in vitro because they form stable binary complexes with DNA through electrostatic interactions. After formation these complexes carry a net positive charge which facilitates their interaction with the net negative charge of a cell s plasma membrane. The lack of in vivo transfectability results from a lack of distribution of the transfection competent complexes because of in situ interactions between the positively charged complexes and the negatively charged extracellular matrix components. Phase I specific aims include: 1. Synthesis and physical characterization of variety of novel cationic amphipaths. 2. Characterize in vitro transfectability using standard cell lines in tissue culture. 3. Correlate physical properties and transfection ability with endosomal function and state. 4. Use specific ligands with an indicated cationic liposome formulation to assay for ligand-dependant transfections in tissue culture. PROPOSED COMMERCIAL APPLICATION This new method of non-viral gene delivery will be commercialized by: 1) selling the technology in the form of reagent kits to biomedical and basic researchers 2) licensing the technology for in vivo gene delivery to pharmaceutical companies for the treatment of genetic diseases or acquired diseases 3) licensing the technology for in vivo gene delivery to pharmaceutical companies for vaccine development.