酶促化学偶联构建核酸适配体靶向型聚酯-g-PEI基因传输载体的研究

Development of novel efficient, safe and targeting non-viral gene carriers is of great significance for the gene therapy of severe diseases. In this project, a carrier polyester-g-PEI with high gene transfection efficiency and low toxicity was first prepared through chemoenzymatic synthesis, using monomers from natural resources. Then the PEI derivative was chemically conjugated through NHS-PEG5K-Mal with an aptamer targeting PSMA antigen in prostate cancers to construct a tumor-targeting gene carrier. Using the transfection of tumor suppressor gene p53 to the p53-deletion tumor cell lines as model, the ability to induce the apoptosis of tumor cells and detailed mechanism were systematically evaluated on both cell and animal levels. In conclusion, the project established a moderate route for preparing gene carriers with no metal residus from natural resources, and would facilitate the development and application of non-viral gene carriers and their clinic application in cancer gene therapy.

新型高效、安全、靶向型非病毒基因传输载体的研究与开发，对于重大疾病的基因治疗具有至关重要的意义。本项目首先从来源于天然可再生资源的功能内酯单体出发，通过酶促化学偶联技术构建高基因转染效率、低毒的聚酯-g-PEI衍生物；然后通过NHS-PEG5K-Mal键合策略，将对前列腺癌抗原PSMA具有高亲和力的核酸适配体与聚酯-g-PEI偶联，构建靶向型基因传输体系；以该材料为载体，介导抑癌基因p53转染p53基因缺失肿瘤细胞系，在细胞和动物水平上评价其诱导肿瘤细胞凋亡的能力及分子机制。本项目的实施，建立了一条温和的、依赖天然可再生资源单体、不含重金属的新型靶向型基因载体材料合成路径，对于推动非病毒基因载体材料的研究开发及肿瘤基因治疗的临床应用等具有重要的意义。

新型高效、安全、靶向型非病毒基因传输载体的研究与开发，对于重大疾病的基因治疗具有至关重要的意义。本项目立足于新型酶促化学偶联聚合技术构建肿瘤靶向基因传输体系，并成功将核酸适配体靶向传输策略应用于抗肿瘤基因传输体系的设计中，开展了以下几方面的研究：从来源于天然可再生资源的功能内酯单体出发，通过酶促化学偶联技术构建高基因转染效率、低毒的聚酯-g-PEI衍生物；通过酶促化学偶联技术，构建了阳离子载体胆固醇-g-聚氨基酯材料，成功实现了miR-23b的高效、稳定、靶向递送，实现了对肿瘤增殖、迁移与浸润的抑制；以核酸适配体为靶向配体，构建了ATP响应型药物与miR-34a共传输体系，实现了恶性肿瘤药物与基因治疗协同作用。项目圆满完成了任务书规定的内容，建立了一条温和的、依赖天然可再生资源单体、不含重金属的新型靶向型基因载体材料合成路径，对于推动非病毒基因载体材料的研究开发及肿瘤基因治疗的临床应用等具有重要的意义。

内容获取失败，请点击重试