Intracellular trafficking and transgene expression of viral and non-viral gene vectors.
The objective of this review is to summarize the critical steps in intracellular trafficking and the principal factors involved in transgene expression by a comparison of viral and non-viral gene vectors. Intracellular trafficking of viral and non-viral gene vectors are reviewed kinetically as well as from the mechanistic point of view. The peptide-dependent specific mechanism of endosomal escape by viral vectors is compared with the non-specific mechanism of non-viral vectors. Regarding the nuclear transport of DNA, a number of recently developed strategies in non-viral vectors such as the application of nuclear localization signals or cell specific transcription factors are summarized in comparison with viral nuclear gene delivery. The molecular mechanisms of transcription and the translation of delivered genes to nucleus are also summarized in view of drug delivery systems. This information is intended to serve as a basis for developing a new gene delivery system for both viral and non-viral gene vectors. Optimizing the gene delivery system by integrating this intracellular trafficking as well as transgene expression will be required in order to develop an efficient and an safe gene delivery system.
Kamiya
H
H
Laboratory for Molecular Design of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Sapporo 060-0812, Japan.
Tsuchiya
H
H
Yamazaki
J
J
Harashima
H
H
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D019076:Transgenes; D014780:Viruses / Q000235:genetics* / Q000378:metabolism*