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Identification of small interfering RNA targeting signal transducer and activator of transcription-6: characterisation and selection of candidates for pre-clinical development

GD Healey, S Zinnen, J Lockridge, I Richards, N Evans, W Walker, William Walker Orcid Logo

J. RNAi Gene Silencing, Volume: 6, Pages: 401 - 10

Swansea University Author: William Walker Orcid Logo

Abstract

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 interfer...

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Published in: J. RNAi Gene Silencing
Published: J. RNAi Gene Silencing 2010
URI: https://cronfa.swan.ac.uk/Record/cronfa10001
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first_indexed 2013-07-23T12:02:35Z
last_indexed 2018-02-09T04:38:32Z
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spelling 2013-09-20T11:19:18.4178799 v2 10001 2012-03-21 Identification of small interfering RNA targeting signal transducer and activator of transcription-6: characterisation and selection of candidates for pre-clinical development 1f736d4178747b6082940868d069894f 0000-0002-1940-5329 William Walker William Walker true false 2012-03-21 BMS 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. Journal Article J. RNAi Gene Silencing 6 401 10 J. RNAi Gene Silencing 31 12 2010 2010-12-31 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2013-09-20T11:19:18.4178799 2012-03-21T16:17:30.0000000 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine GD Healey 1 S Zinnen 2 J Lockridge 3 I Richards 4 N Evans 5 W Walker 6 William Walker 0000-0002-1940-5329 7
title Identification of small interfering RNA targeting signal transducer and activator of transcription-6: characterisation and selection of candidates for pre-clinical development
spellingShingle Identification of small interfering RNA targeting signal transducer and activator of transcription-6: characterisation and selection of candidates for pre-clinical development
William Walker
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_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_sort Identification of small interfering RNA targeting signal transducer and activator of transcription-6: characterisation and selection of candidates for pre-clinical development
author_id_str_mv 1f736d4178747b6082940868d069894f
author_id_fullname_str_mv 1f736d4178747b6082940868d069894f_***_William Walker
author William Walker
author2 GD Healey
S Zinnen
J Lockridge
I Richards
N Evans
W Walker
William Walker
format Journal article
container_title J. RNAi Gene Silencing
container_volume 6
container_start_page 401
publishDate 2010
institution Swansea University
publisher J. RNAi Gene Silencing
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 0
active_str 0
description 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.
published_date 2010-12-31T03:10:37Z
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score 11.012678

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