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基因递送系统的进展

Advances in Gene Delivery Systems.

作者信息

Kamimura Kenya, Suda Takeshi, Zhang Guisheng, Liu Dexi

机构信息

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

出版信息

Pharmaceut Med. 2011 Oct 1;25(5):293-306. doi: 10.2165/11594020-000000000-00000.

Abstract

The transfer of genes into cells, both in vitro and in vivo, is critical for studying gene function and conducting gene therapy. Methods that utilize viral and nonviral vectors, as well as physical approaches, have been explored. Viral vector-mediated gene transfer employs replication-deficient viruses such as retro-virus, adenovirus, adeno-associated virus and herpes simplex virus. A major advantage of viral vectors is their high gene delivery efficiency. The nonviral vectors developed so far include cationic liposomes, cationic polymers, synthetic peptides and naturally occurring compounds. These nonviral vectors appear to be highly effective in gene delivery to cultured cells in vitro but are significantly less effective in vivo. Physical methods utilize mechanical pressure, electric shock or hydrodynamic force to transiently permeate the cell membrane to transfer DNA into target cells. They are simpler than viral- and nonviral-based systems and highly effective for localized gene delivery. The past decade has seen significant efforts to establish the most desirable method for safe, effective and target-specific gene delivery, and good progress has been made. The objectives of this review are to (i) explain the rationale for the design of viral, nonviral and physical methods for gene delivery; (ii) provide a summary on recent advances in gene transfer technology; (iii) discuss advantages and disadvantages of each of the most commonly used gene delivery methods; and (iv) provide future perspectives.

摘要

基因导入细胞,无论在体外还是体内,对于研究基因功能和进行基因治疗都至关重要。人们已经探索了利用病毒载体、非病毒载体以及物理方法的途径。病毒载体介导的基因转移采用复制缺陷型病毒,如逆转录病毒、腺病毒、腺相关病毒和单纯疱疹病毒。病毒载体的一个主要优点是其高基因传递效率。目前开发的非病毒载体包括阳离子脂质体、阳离子聚合物、合成肽和天然化合物。这些非病毒载体在体外向培养细胞的基因传递中似乎非常有效,但在体内的效果则明显较差。物理方法利用机械压力、电击或流体动力来短暂穿透细胞膜,将DNA转移到靶细胞中。它们比基于病毒和非病毒的系统更简单,并且对局部基因传递非常有效。在过去十年中,人们为建立最理想的安全、有效且靶向特异性基因传递方法付出了巨大努力,并取得了良好进展。本综述的目的是:(i)解释设计病毒、非病毒和物理基因传递方法的基本原理;(ii)总结基因转移技术的最新进展;(iii)讨论每种最常用基因传递方法的优缺点;(iv)提供未来展望。

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