基因治疗输送屏障和输送载体研究.PDFVIP

现代生物医学进展 Progress in Modern Biomedicine Vol.14 NO.1 JAN.2014 177 DOI: 10.13241/ki.pmb.2014.01.046 基因治疗的输送屏障及输送载体的研究* 吕 楠 马柳青 陈 顺 兰维华 黄袭雯 袁伟恩 (上海交通大学药学院 上海200240) 摘要：基因治疗是将可具有治疗性的基因导入病变细胞以达到治疗遗传性疾病或获得性功能缺损疾病的治疗手段，是一种极具 潜力的新型治疗方法。然而基因治疗面临着一系列临床应用障碍，其中缺乏理想的基因输送载体是首要问题。绝大多数基因治疗 方案受困缺乏安全有效的基因输送手段，载体要达到目的地发挥作用，需要克服一系列复杂的体内生物屏障，包括细胞外屏障和 细胞内屏障。目前基因输送载体主要分为病毒载体和非病毒载体，其中病毒载体天然进化至可进入宿主细胞，具有输送效率高， 靶向性好的特点，但存在长期安全性的缺点。非病毒载体主要包括阳离子脂质体和阳离子聚合物，由于易于制备和无免疫原性、 安全性好，被认为是更有潜力的输送载体，是目前研究的重点。本文结合基因治疗输送屏障的理论基础及临床研究，对基因输送 载体系统的现状进行了综述。 关键词：基因治疗；输送屏障；非病毒载体 R45 A 1673-6273 2014 0 1-177-03 中图分类号： 文献标识码： 文章编号： （ ） Study on Gene Delivery Barries and Vectors for Therapy* Gene therapy, i.e., the expression in cells of genetic material with therapeutic activity, holds great promise for the treatment of a wide range of both inherited and acquired diseases. The lack of delivery system becomes the only key obstacle for bringing DNA/siRNA to clinical therapy. Maj ority of clinical proj ects suffer from lacking of safe and vectors, in order to target and play its role, carries need to overcome a series of complex bio-barriers in the body, including extracellular barriers and cellular barriers. Between the two maj or systems for gene delivery, viral vectors take advantage of the facile integration of the gene of interest into the host and high probability of its long-term expression but are plagued by safety concerns. Non-viral vectors, including cationic liposome and cationic polymer, have been proposed as a more promsing alternatives to viral vectors because they avoid the inherent immunogenicity and production problems that are seen when viral systems are used.This paper summarizes basic principles and clinical researchs in gene therapy, giving an overview of gene therapy vector sy