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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

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

Swansea University Author: Walker, William

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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spelling 2013-09-20T11:19:18Z 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 William Walker William Walker true 0000-0002-1940-5329 false 1f736d4178747b6082940868d069894f 28d7e547bc0f7d7d9f269fbb1a48e34a loNwgpSQDy5qZ83C10Fw8tyvqZQRJmUl2lxhnzSZE7o= 2012-03-21 PMSC 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 0 0 2010 2010-01-01 Swansea University Medical School Medicine CMED PMSC 2013-09-20T11:19:18Z 2012-03-21T16:17:30Z Swansea University Medical School Medicine GD Healey 1 S Zinnen 2 J Lockridge 3 I Richards 4 N Evans 5 W Walker 6
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
Walker, William
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_***_Walker, William
author Walker, William
author2 GD Healey
S Zinnen
J Lockridge
I Richards
N Evans
W 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 Swansea University Medical School
hierarchytype
hierarchy_top_id swanseauniversitymedicalschool
hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
document_store_str 0
active_str 1
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 2010-01-01T04:51:28Z
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