Akita Hidetaka, Harashima Hideyoshi
CREST Japan Science and Technology Agency (JST), Japan.
Expert Opin Drug Deliv. 2008 Aug;5(8):847-59. doi: 10.1517/17425247.5.8.847.
Low transfection efficiency is an obstacle to the clinical use of non-viral gene vectors. Effective non-viral vectors require the ability to control intracellular trafficking of gene vectors for the delivery of exogenous DNA to the nucleus.
To overcome multiple intracellular barriers, various types of devices must be integrated into one nano-particle so that each device performs its function at the appropriate location at the desired time. Such a strategy requires an understanding, based on quantitative information, of the rate-limiting processes that hinder intracellular trafficking.
In this review, advancements in the development of multifunctional envelope-type nano-devices (MEND) are discussed. In particular, a novel method to quantitatively evaluate the rate-limiting steps in intracellular trafficking, based on a comparison of viral and non-viral gene-delivery systems, is described.
MENDs are useful to integrate various kinds of devices to overcome intracellular barriers into one particle. Comparison of intracellular trafficking between adenoviruses and non-viral vectors indicates that a postnuclear delivery process is an important rate-limiting step for efficient transfection with non-viral vectors.
低转染效率是阻碍非病毒基因载体临床应用的一个障碍。有效的非病毒载体需要具备控制基因载体细胞内运输的能力，以便将外源DNA递送至细胞核。
为克服多种细胞内障碍，必须将各类装置整合到一个纳米颗粒中，使每个装置能在所需时间的适当位置发挥其功能。这种策略需要基于定量信息来了解阻碍细胞内运输的限速过程。
在本综述中，讨论了多功能包膜型纳米装置（MEND）的研发进展。特别描述了一种基于病毒和非病毒基因递送系统比较来定量评估细胞内运输限速步骤的新方法。
MEND有助于将克服细胞内障碍的各类装置整合到一个颗粒中。腺病毒与非病毒载体细胞内运输的比较表明，核后递送过程是高效转染非病毒载体的一个重要限速步骤。
