Advances in non-viral gene delivery: using multifunctional envelope-type nano-device.
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.


CONCLUSIONS
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.
Akita
Hidetaka
H
CREST Japan Science and Technology Agency (JST), Japan.
Harashima
Hideyoshi
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008954:Models, Biological; D049329:Nanostructures / Q000737:chemistry*; D010957:Plasmids; D014162:Transfection / Q000379:methods*