Abstract
Small polybasic peptides derived from the transduction domains of certain proteins, such as the third α-helix of the Antennapedia (Antp) homeodomain, can cross the cell membrane through a receptor-independent mechanism. These cell-permeable molecules have been used as 'Trojan horses' to introduce biologically active cargo molecules such as DNA, peptides or proteins into cells. Using these cell-permeable peptides, we have developed an efficient and simple method to increase virally mediated gene delivery and protein expression in vitro and in vivo. Here, we show that cell-permeable peptides increase viral cell entry, improve gene expression at reduced titers of virus and improve efficacy of therapeutically relevant genes in vivo.
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Acknowledgements
We thank J. Pober and A. Bothwell for the Ret-GFP virus. This work is supported by grants from the US National Institutes of Health (RO1 HL57665, HL61371 and HL64793) to W.C.S. J.P.G. was supported by a fellowship from the Canadian Institutes of Health Research and R.S.S. was funded by a Wellcome Prize Traveling Research Fellowship.
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Gratton, JP., Yu, J., Griffith, J. et al. Cell-permeable peptides improve cellular uptake and therapeutic gene delivery of replication-deficient viruses in cells and in vivo. Nat Med 9, 357–362 (2003). https://doi.org/10.1038/nm835
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DOI: https://doi.org/10.1038/nm835
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