Open AccessEvaluation of nasal epithelium sampling as a tool in the preclinical development of siRNA‐based therapeutics for asthma
Author(s) -
Healey Gareth D,
Evans Neil,
Hopkin Julian M,
Davies Gwyneth,
Walker William
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12014
Subject(s) - rna , immunology , small interfering rna , asthma , medicine , pathogenesis , cell , cancer research , biology , gene , genetics , biochemistry
Abstract The development of si RNA ‐based asthma therapeutics is currently hampered by a paucity of relevant biomarkers and the need to ascertain tissue‐specific gene targeting in the context of active disease. Epithelial STAT 6 expression is fundamental to asthma pathogenesis in which inflammatory changes are found throughout the respiratory tract. Therefore, to improve preclinical evaluation, we tested the efficacy of STAT 6‐targeting si RNA within nasal epithelial cells ( NEC 's) obtained from asthmatic and non‐asthmatic donors. STAT 6 expression was invariant in both donor groups and amenable to suppression by si RNA treatment. In addition, STAT 6 m RNA was also suppressible by apically delivered si RNA treatment in comparative differentiated nasal epithelial cell‐line monolayer cultures. Analysis of donor NEC 's showed consistent elevation in CCL 26 (eotaxin‐3) m RNA within the asthmatic group suggesting potential as a relevant biomarker. Furthermore, targeting of STAT 6 with si RNA attenuated IL ‐13‐driven CCL 26 expression in these cells, pointing to the utility of this approach in preclinical testing. Finally, si RNA ‐mediated suppression of STAT 6 was independent of donor disease phenotype or epithelial cell differentiation status, signifying therapeutic potential.