The therapeutic application of siRNA (short interfering RNA) shows promise as an alternative approach to small-molecule inhibitors for the treatment of human disease. However, the major obstacle to its use has been the difficulty in delivering these large anionic molecules in vivo. A potential approach to solving this problem is the chemical conjugation of siRNA to the cationic CPPs (cell-penetrating peptides), Tat-(48–60) (transactivator of transcription) and penetratin, which have been shown previously to mediate protein and peptide delivery in a host of animal models. In this transaction, we review recent studies on the utility of siRNA for the investigation of protein function in the airways/lung. We show that, despite previous studies showing the utility of cationic CPPs in vitro, conjugation of siRNA to Tat-(48–60) and penetratin failed to increase residual siRNA-mediated knockdown of p38 MAPK (mitogen-activated protein kinase) (MAPK14) mRNA in mouse lung in vivo. Significantly, we will also discuss potential non-specific actions and the induction of immunological responses by CPPs and their conjugates and how this might limit their application for siRNA-mediated delivery in vivo.
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August 2007
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Conference Article|
July 20 2007
Cell-penetrating-peptide-mediated siRNA lung delivery
S.A. Moschos;
S.A. Moschos
1Biopharmaceutics Research Group, Airways Disease, National Heart and Lung Institute, Imperial College London, London SW3 6LY, U.K.
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A.E. Williams;
A.E. Williams
1Biopharmaceutics Research Group, Airways Disease, National Heart and Lung Institute, Imperial College London, London SW3 6LY, U.K.
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M.A. Lindsay
M.A. Lindsay
1
1Biopharmaceutics Research Group, Airways Disease, National Heart and Lung Institute, Imperial College London, London SW3 6LY, U.K.
1To whom correspondence should be addressed (email m.lindsay@imperial.ac.uk).
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Publisher: Portland Press Ltd
Received:
April 24 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 807–810.
Article history
Received:
April 24 2007
Citation
S.A. Moschos, A.E. Williams, M.A. Lindsay; Cell-penetrating-peptide-mediated siRNA lung delivery. Biochem Soc Trans 1 August 2007; 35 (4): 807–810. doi: https://doi.org/10.1042/BST0350807
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