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siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects
Small interfering RNA (siRNA) is widely used to specifically silence target gene expression, but its microRNA (miRNA)-like function inevitably suppresses hundreds of off-targets. Recently, complete elimination of the off-target repression has been achieved by introducing an abasic nucleotide to the...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6183071/ https://www.ncbi.nlm.nih.gov/pubmed/30321353 http://dx.doi.org/10.1093/database/bay109 |
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author | Park, Jongyeun Ahn, Seung Hyun Cho, Kwang Moon Gu, Dowoon Jang, Eun-Sook Chi, Sung Wook |
author_facet | Park, Jongyeun Ahn, Seung Hyun Cho, Kwang Moon Gu, Dowoon Jang, Eun-Sook Chi, Sung Wook |
author_sort | Park, Jongyeun |
collection | PubMed |
description | Small interfering RNA (siRNA) is widely used to specifically silence target gene expression, but its microRNA (miRNA)-like function inevitably suppresses hundreds of off-targets. Recently, complete elimination of the off-target repression has been achieved by introducing an abasic nucleotide to the pivot (position 6; siRNA-6Ø), of which impaired base pairing destabilizes transitional nucleation (positions 2–6). However, siRNA-6Ø varied in its conservation of on-target activity (∼80–100%), demanding bioinformatics to discover the principles underlying its on-target efficiency. Analyses of miRNA–target interactions (Ago HITS-CLIP) showed that the stability of transitional nucleation correlated with the target affinity of RNA interference. Furthermore, interrogated analyses of siRNA screening efficiency, experimental data and broadly conserved miRNA sequences showed that the free energy of transitional nucleation (positions 2–5) in siRNA-6Ø required the range of stability for effective on-target activity (−6 ≤ ΔG[2:5] ≤ −3.5 kcal mol(−1)). Taking into consideration of these features together with locations, guanine-cytosine content (GC content), nucleotide stretches, single nucleotide polymorphisms and repetitive elements, we implemented a database named ‘siAbasic’ that provided the list of potent siRNA-6Ø sequences for most of human and mouse genes (≥ ∼95%), wherein we experimentally validated some of their therapeutic potency. siAbasic will aid to ensure potency of siRNA-6Ø sequences without concerning off-target effects for experimental and clinical purposes. |
format | Online Article Text |
id | pubmed-6183071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61830712018-10-25 siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects Park, Jongyeun Ahn, Seung Hyun Cho, Kwang Moon Gu, Dowoon Jang, Eun-Sook Chi, Sung Wook Database (Oxford) Original Article Small interfering RNA (siRNA) is widely used to specifically silence target gene expression, but its microRNA (miRNA)-like function inevitably suppresses hundreds of off-targets. Recently, complete elimination of the off-target repression has been achieved by introducing an abasic nucleotide to the pivot (position 6; siRNA-6Ø), of which impaired base pairing destabilizes transitional nucleation (positions 2–6). However, siRNA-6Ø varied in its conservation of on-target activity (∼80–100%), demanding bioinformatics to discover the principles underlying its on-target efficiency. Analyses of miRNA–target interactions (Ago HITS-CLIP) showed that the stability of transitional nucleation correlated with the target affinity of RNA interference. Furthermore, interrogated analyses of siRNA screening efficiency, experimental data and broadly conserved miRNA sequences showed that the free energy of transitional nucleation (positions 2–5) in siRNA-6Ø required the range of stability for effective on-target activity (−6 ≤ ΔG[2:5] ≤ −3.5 kcal mol(−1)). Taking into consideration of these features together with locations, guanine-cytosine content (GC content), nucleotide stretches, single nucleotide polymorphisms and repetitive elements, we implemented a database named ‘siAbasic’ that provided the list of potent siRNA-6Ø sequences for most of human and mouse genes (≥ ∼95%), wherein we experimentally validated some of their therapeutic potency. siAbasic will aid to ensure potency of siRNA-6Ø sequences without concerning off-target effects for experimental and clinical purposes. Oxford University Press 2018-10-12 /pmc/articles/PMC6183071/ /pubmed/30321353 http://dx.doi.org/10.1093/database/bay109 Text en © The Author(s) 2018. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Park, Jongyeun Ahn, Seung Hyun Cho, Kwang Moon Gu, Dowoon Jang, Eun-Sook Chi, Sung Wook siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects |
title |
siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects
|
title_full |
siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects
|
title_fullStr |
siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects
|
title_full_unstemmed |
siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects
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title_short |
siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects
|
title_sort | siabasic: a comprehensive database for potent sirna-6ø sequences without off-target effects |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6183071/ https://www.ncbi.nlm.nih.gov/pubmed/30321353 http://dx.doi.org/10.1093/database/bay109 |
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