A novel program to design siRNAs simultaneously effective to highly variable virus genomes

A major concern of antiviral therapy using small interfering RNAs (siRNAs) targeting RNA viral genome is high sequence diversity and mutation rate due to genetic instability. To overcome this problem, it is indispensable to design siRNAs targeting highly conserved regions. We thus designed CAPSID (C...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-07, Vol.384 (4), p.431-435
Main Authors: Lee, Hui Sun, Ahn, Jeonghyun, Jun, Eun Jung, Yang, Sanghwa, Joo, Chul Hyun, Kim, Yoo Kyum, Lee, Heuiran
Format: Article
Language:English
Subjects:
Animals
Antiviral activity
CAPSID
Cercopithecus aethiops
Computational Biology - methods
Enterovirus
Enterovirus B, Human - classification
Enterovirus B, Human - genetics
Enterovirus Infections - therapy
Genetic instability
Genome, Viral
HeLa Cells
Humans
RNA, Small Interfering - chemistry
RNA, Small Interfering - genetics
Sequence Analysis, RNA - methods
Sequence diversity
Small-interfering RNA
Software
Vero Cells
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Summary:A major concern of antiviral therapy using small interfering RNAs (siRNAs) targeting RNA viral genome is high sequence diversity and mutation rate due to genetic instability. To overcome this problem, it is indispensable to design siRNAs targeting highly conserved regions. We thus designed CAPSID (Convenient Application Program for siRNA Design), a novel bioinformatics program to identify siRNAs targeting highly conserved regions within RNA viral genomes. From a set of input RNAs of diverse sequences, CAPSID rapidly searches conserved patterns and suggests highly potent siRNA candidates in a hierarchical manner. To validate the usefulness of this novel program, we investigated the antiviral potency of universal siRNA for various Human enterovirus B (HEB) serotypes. Assessment of antiviral efficacy using Hela cells, clearly demonstrates that HEB-specific siRNAs exhibit protective effects against all HEBs examined. These findings strongly indicate that CAPSID can be applied to select universal antiviral siRNAs against highly divergent viral genomes.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.04.143