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Chapter 5
Mucosal Delivery of RNAi Therapeutics
Borja Ballarín González , Ebbe Bech Nielsen , Troels Bo Thomsen ,
and Kenneth A. Howard
Abstract
The effectiveness of RNA interference-based drugs is dependent on
accumulation at the target site in therapeutically relevant amounts. Local adminis-
tration to the mucosal surfaces lining the respiratory, gastrointestinal and genitouri-
nary tracts allows access into diseased areas without the necessity to overcome
serum nuclease degradation, rapid renal and hepatic clearance and non-specific tis-
sue accumulation associated with systemic delivery. This work describes RNAi
therapeutics focused on pulmonary, oral, rectal and intravaginal routes of adminis-
tration. Mucosal barrier components including site variations and delivery consid-
erations are addressed in order to design an effective mucosal delivery strategy.
5.1
Introduction
Regulation of cellular gene expression by harnessing the natural process of RNA
interference (RNAi) offers an exciting gene medicine approach [
1,
2
] . Post-
transcriptional silencing occurs by mRNA engagement with small interfering RNA
(siRNA) or microRNA (miRNA) facilitated by complementary base pairing [
3
] .
Gene specificity coupled with the capability for externally introduced synthetic
siRNA and miRNA to be recruited into the cellular RNAi pathway provides the
rational for RNAi drug development. A greater understanding of the molecular
mechanism of RNAi has resulted in a wide repertoire of potential RNAi drugs
involved in the RNAi pathway cascade that offers diverse therapeutic options.
B. Ballarin González • E. B. Nielsen • T. B. Thomsen • K. A. Howard, Ph.D. (
*
)
Department of Molecular Biology and Genetics, Interdisciplinary Nanoscience Center,
Aarhus University , Gustav Wieds Vej 14, Building 1593 , 8000 Aarhus C , Denmark
e-mail: kenh@inano.au.dk
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