Cell-penetrating-peptide-mediated siRNA lung delivery.

Moschos, Sterghios, Williams, Andrew Evan and Lindsay, Mark (2007) Cell-penetrating-peptide-mediated siRNA lung delivery. Biochemical Society Transactions, 35 (4). pp. 807-810. ISSN 0300-5127

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	lungp38 mitogen-activated protein kinase (p38 MAPK)penetratinshort interfering RNA (siRNA)transactivator of transcription (Tat)
Subjects:	B200 Pharmacology, Toxicology and Pharmacy C700 Molecular Biology, Biophysics and Biochemistry
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Sterghios Moschos
Date Deposited:	24 Oct 2016 08:52
Last Modified:	12 Oct 2019 17:30
URI:	http://nrl.northumbria.ac.uk/id/eprint/28146

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