Identification of small interfering RNA targeting Signal Transducer and Activator of Transcription 6: Characterisation and selection of candidates for pre-clinical development

<p style="text-align:justify;">The interleukin (IL)-13 pathway and its associated transcription factor, signal transducer and activator of transcription 6 (STAT6), have been clearly implicated in the pathogenesis of bronchial asthma. We have developed a system to effectively screen t...

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Main Authors: Healey, G, Zinnen, S, Lockridge, J, Richard, I, Evans, N, Walker, W
Format: Journal article
Published: Library Publishing Media 2010
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author Healey, G
Zinnen, S
Lockridge, J
Richard, I
Evans, N
Walker, W
author_facet Healey, G
Zinnen, S
Lockridge, J
Richard, I
Evans, N
Walker, W
author_sort Healey, G
collection OXFORD
description <p style="text-align:justify;">The interleukin (IL)-13 pathway and its associated transcription factor, signal transducer and activator of transcription 6 (STAT6), have been clearly implicated in the pathogenesis of bronchial asthma. We have developed a system to effectively screen the STAT6 gene for targeting with small interfering (si) RNA molecules. By incorporating an in silico and in vitro screening system we were able to identify fourteen siRNA molecules suitable for pre-clinical drug development. Furthermore, we were able to demonstrate that modification of certain siRNAs, designed to improve in vivo longevity, was possible without significant loss of target knockdown efficacy and that the siRNA produced by our selection process did not induce demonstrable interferon responses. These data suggest that several STAT6-targeting siRNA suitable for pre-clinical development are available for potential use in the treatment of asthma.</p>
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spelling oxford-uuid:6b78f0ab-b01a-4fce-9ad6-f15e2a5e65d92022-03-26T19:04:15ZIdentification of small interfering RNA targeting Signal Transducer and Activator of Transcription 6: Characterisation and selection of candidates for pre-clinical developmentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6b78f0ab-b01a-4fce-9ad6-f15e2a5e65d9Symplectic Elements at OxfordLibrary Publishing Media2010Healey, GZinnen, SLockridge, JRichard, IEvans, NWalker, W<p style="text-align:justify;">The interleukin (IL)-13 pathway and its associated transcription factor, signal transducer and activator of transcription 6 (STAT6), have been clearly implicated in the pathogenesis of bronchial asthma. We have developed a system to effectively screen the STAT6 gene for targeting with small interfering (si) RNA molecules. By incorporating an in silico and in vitro screening system we were able to identify fourteen siRNA molecules suitable for pre-clinical drug development. Furthermore, we were able to demonstrate that modification of certain siRNAs, designed to improve in vivo longevity, was possible without significant loss of target knockdown efficacy and that the siRNA produced by our selection process did not induce demonstrable interferon responses. These data suggest that several STAT6-targeting siRNA suitable for pre-clinical development are available for potential use in the treatment of asthma.</p>
spellingShingle Healey, G
Zinnen, S
Lockridge, J
Richard, I
Evans, N
Walker, W
Identification of small interfering RNA targeting Signal Transducer and Activator of Transcription 6: Characterisation and selection of candidates for pre-clinical development
title Identification of small interfering RNA targeting Signal Transducer and Activator of Transcription 6: Characterisation and selection of candidates for pre-clinical development
title_full Identification of small interfering RNA targeting Signal Transducer and Activator of Transcription 6: Characterisation and selection of candidates for pre-clinical development
title_fullStr Identification of small interfering RNA targeting Signal Transducer and Activator of Transcription 6: Characterisation and selection of candidates for pre-clinical development
title_full_unstemmed Identification of small interfering RNA targeting Signal Transducer and Activator of Transcription 6: Characterisation and selection of candidates for pre-clinical development
title_short Identification of small interfering RNA targeting Signal Transducer and Activator of Transcription 6: Characterisation and selection of candidates for pre-clinical development
title_sort identification of small interfering rna targeting signal transducer and activator of transcription 6 characterisation and selection of candidates for pre clinical development
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