摘要
安全有效的基因载体对于基因治疗有着重要的潜在价值。相对于病毒性基因载体,化学合成的载体具有低免疫原性,易于大规模生产和生产成本较低的特性,因而受到越来越多的关注,但是非病毒基因载体在转染效率和选择性方面有一定的限制性,当前的主要研究工作集中在这两方面。基于环糊精构建的基因载体,可以有效地提供基因载体的立体构象和功能性的选择性。作为FDA批准的生物材料,环糊精具有无毒和生物降解性,其不但可以保护基因,避免在体内降解,同时有助于通过细胞膜,进入细胞内达到基因转染的作用。环糊精具有大量可修饰的羟基基团,因此对环糊精修饰不但可以通过主客体作用构建超分子体系,并且可以作为多官能团核形成星状高分子,被广泛应用于制备低毒、可降解、靶向性和高效率的转基因载体。目前,环糊精修饰的非病毒正离子载体转移siRNA,已经成功进行了色素瘤的临床试验,取得了很好的治疗效果,表明了环糊精非病毒载体的巨大应用前景。本文对基于环糊精基因载体的最新研究进展进行了综述,详细介绍了基于环糊精的超分子自组装构建的聚轮烷型、侧链分子识别型的基因载体,以及基于环糊精多羟基构型而构建的星型聚合物基因载体和树枝状基因载体,并对环糊精基因载体的优越性和未来应用做了相应的介绍。
Safe and efficient delivery of nucleic acid constructs to target cells has great potential for the treatment of genetic diseases. Non-viral gene delivery has attracted considerable attention because of large-scale production, immunogenicity and safety concerns. Whereas, non-viral gene delivery still suffered from low transfection efficiency and lack of selectivity, which is the main target on this field. The gene delivery based on cyclodextrin （CD） can offer the possibility for construction of various multi-functional gene deliveries. As a FDA approved bin-material, CDs have been extensively used for gene delivery because of their ability to stabilize the nucleic acids in biological media and their ability to destabilize and permeate biological membranes and for obviating undesirable side effects. CD is not only a widely used host molecule capable of internalizing vip molecules in water, but also a core with abundant OH based on CD＇ s host-vip interaction and core structure. Recently, CD modified gene delivery has achieved to the clinic test with remarkable result, showing great potential application. In this review the newest development of the gene delivery based on cyclodextrin is summarized. The article provides detail information about the rotaxanes type, side-chain type, star-shape type and branched type deliveries of nucleic acid. Furthermore, the advantage of CD based gene delivery is emphasized herein, which has been applied in clinical test.
出处
《化学进展》
SCIE
CAS
CSCD
北大核心
2014年第2期375-384,共10页
Progress in Chemistry
基金
上海市东方学者资助
国家自然科学基金项目(No.21102088
21174081)
浦江学者(12PJ1403400)
湖南省教育厅科研课题(10C0268)资助~~
关键词
环糊精
超分子
自组装
基因载体
cyclodextrin
supramolecule
self-assembly
gene delivery
