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基于阳离子脂质体/胶束的非病毒载体系统用于基因治疗的问题。

The problem with cationic liposome/micelle-based non-viral vector systems for gene therapy.

作者信息

Miller Andrew D

机构信息

Imperial College Genetic Therapies Centre, Imperial College London, London, UK.

出版信息

Curr Med Chem. 2003 Jul;10(14):1195-211. doi: 10.2174/0929867033457485.

Abstract

Gene therapy research is in crisis owing to the lack of acceptable vector systems to deliver nucleic acids to patients for therapy. Viral vectors are efficient but currently appear to be too dangerous for routine clinical use. Synthetic non-viral vectors are inherently much safer but are currently not efficient enough to be clinically viable. The solution for gene therapy lies with improved synthetic non-viral vectors based upon well-found platform technologies and a thorough understanding of the barriers to efficient gene delivery and expression (transfection) relevant to clinical applications of interest. In this review, the current status and prospects for cationic liposome/micelle-based synthetic non-viral vector systems are discussed including a description of the barriers to efficient transfection, a summary of the main structure/activity studies and mention of ternary cationic liposome/micelle-nucleic acid (LD) systems. The review culminates with a description of two promising cationic liposome/micelle-based non-viral vector platform systems known as liposome:mu:DNA (LMD) and stabilised plasmid-lipid particles (SPLP) that should create a real opportunity for the development of clinically viable synthetic vector systems within the next few years.

摘要

由于缺乏可接受的载体系统将核酸递送至患者体内进行治疗,基因治疗研究正处于危机之中。病毒载体效率高,但目前对于常规临床应用而言似乎过于危险。合成非病毒载体本质上要安全得多,但目前效率还不够高,无法用于临床。基因治疗的解决方案在于基于成熟的平台技术改进合成非病毒载体,并深入了解与感兴趣的临床应用相关的有效基因递送和表达(转染)障碍。在这篇综述中,讨论了基于阳离子脂质体/胶束的合成非病毒载体系统的现状和前景,包括对有效转染障碍的描述、主要结构/活性研究的总结以及对三元阳离子脂质体/胶束 - 核酸(LD)系统的提及。综述最后描述了两种有前景的基于阳离子脂质体/胶束的非病毒载体平台系统,即脂质体:μ:DNA(LMD)和稳定化质粒 - 脂质颗粒(SPLP),它们有望在未来几年为开发临床上可行的合成载体系统创造真正的机会。

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