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Trends Pharmacol Sci. 2009 Jul;30(7):341-5. doi: 10.1016/ Epub 2009 Jun 21.

siRNA delivery using peptide transduction domains.

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  • 1Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0686, USA.


Targeting mRNA degradation by short interfering RNAs (siRNAs) offers great potential to treat multiple diseases. However, owing to their high molecule size and strong anionic charge, siRNAs cannot pass through the highly regulated and restricted plasma membrane. To overcome these problems, many approaches have been developed and applied in clinical trial. However, other siRNA delivery systems are still required to enhance the siRNA uptake. Over the past 20 years, peptide transduction domains (PTDs) have been discovered that can cross the cellular membrane by themselves despite their high molecule size. PTDs have been used for the delivery of a wide range of molecules including peptides, proteins and antisense oligonucleotides and applied in vivo systems. Here, we review siRNA delivery using PTDs in vitro and in vivo and discuss its potential for use in siRNA-based therapy.

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