Cell-penetrating-peptide-mediated siRNA lung delivery. (20th July 2007)

• Record Type: Journal Article
• Authors: Moschos, S.A.; Williams, A.E.; Lindsay, M.A.
• Is Part Of: Biochemical Society transactions. Volume 35:Number 4(2007)
• Page Start: 807
• Page End: 810
• Publication Date: 2007-07-20
• Subjects: lung -- p38 mitogen-activated protein kinase (p38 MAPK) -- penetratin -- short interfering RNA (siRNA) -- transactivator of transcription (Tat); Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0350807
• Languages: English
• ISSNs: 0300-5127

Abstract

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 .