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Intracellular trafficking of retroviral vectors: obstacles and advances

Gene Therapy volume 12, pages 1667–1678 (2005)Cite this article

Abstract

Retroviruses are efficient vehicles for delivering transgenes in vivo. Their ability to integrate into the host genome, providing a permanent imprint of their genes in the host, is a key asset for gene therapy. Furthermore, the lentivirus subset of retroviruses can infect nondividing as well as dividing cells. This expands the cell types capable of gene therapy, driving the development of lentiviral vectors. However, the precise mechanisms used by different retroviruses to efficiently deliver their genes into cell nuclei remains largely unclear. Understanding these molecular mechanisms may reveal features to improve the efficacy of current retroviral vectors. Moreover, this knowledge may expose elements pliable to other gene therapy vehicles to improve their in vivo performance and circumvent the biosafety concerns of using retroviral vectors. Therefore, the mechanisms underlying the early trafficking of retroviral vectors in host cells are reviewed here, as understood from studying the native retroviruses. Events after virus entry up to nuclear delivery of the viral cDNA are discussed. Cellular obstacles faced by these retroviral vectors and how they advance beyond these barriers is emphasized.

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Acknowledgements

This work was supported through the National Institutes of Health RO1 Grant AI47770 to TJ Hope.

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Anderson, J., Hope, T. Intracellular trafficking of retroviral vectors: obstacles and advances. Gene Ther 12, 1667–1678 (2005). https://doi.org/10.1038/sj.gt.3302591

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