Abstract
Background: 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. Objective: 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. Methods: 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. Conclusion: 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.
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