Luten Jordy, van Nostrum Cornelus F, De Smedt Stefaan C, Hennink Wim E
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands.
J Control Release. 2008 Mar 3;126(2):97-110. doi: 10.1016/j.jconrel.2007.10.028. Epub 2007 Dec 4.
Gene therapy holds a great promise for the treatment of acquired and inherited diseases with a genetic origin that are currently incurable. Non-viral gene delivery systems are gaining recognition as an alternative to viral gene vectors for their potential in avoiding immunogenicity and toxicity problems inherently associated with the use of viral systems. Many cationic polymers have been studied both in vitro and in vivo for gene delivery purposes. However, in recent years there has been a focus on biodegradable carrier systems. The potential advantage of biodegradable carriers as compared to their non-degradable counterparts is their reduced toxicity and the avoidance of accumulation of the polymer in the cells after repeated administration. Also, the degradation of the polymer can be used as a tool to release the plasmid DNA into the cytosol. In this article the recent results obtained with two classes of degradable gene delivery systems, namely those based on water-soluble cationic polymers and on micro- and nanoparticles will be summarized and discussed.
基因治疗对于治疗目前无法治愈的、具有遗传起源的后天性和遗传性疾病具有巨大的前景。非病毒基因递送系统因其在避免与使用病毒系统固有相关的免疫原性和毒性问题方面的潜力，正逐渐被认可为病毒基因载体的替代方案。许多阳离子聚合物已在体外和体内进行了基因递送目的的研究。然而，近年来人们一直关注可生物降解的载体系统。与不可降解的载体相比，可生物降解载体的潜在优势在于其降低的毒性以及避免聚合物在重复给药后在细胞中积累。此外，聚合物的降解可作为将质粒DNA释放到细胞质中的一种手段。在本文中，将总结和讨论两类可降解基因递送系统，即基于水溶性阳离子聚合物以及基于微米和纳米颗粒的系统所获得的最新结果。
