NDLI: 3Si: a computer program for the optimal design of short interfering RNA (siRNA) for gene silencing

Content Provider	IEEE Xplore Digital Library
Author	WeiPing Chen Wei Zha Terry Cox Xiujun Zhao Russell, P.
Copyright Year	2004
Description	Author affiliation: Nat. Eye Inst., Nat. Inst. of Health, Reston, VA, USA (WeiPing Chen)
Abstract	siRNA is a powerful technique for gene silencing. However, it is still not clear how to accurately determine an effective gene targeting region for siRNA. It is also controversial if the targeted mRNA secondary structure would have a significant impact on the gene silencing by the siRNA. Understanding the relationship between the secondary structure and gene silencing by siRNA could help in high throughput function-based genetic screens and for development of therapeutic tools. Our hypothesis is that the selection of a single-stranded region as the target region should increase the efficiency of siRNA silencing. For the first time, a formula and a computer program were developed to select the single-stranded regions for siRNA silencing. We statistically analyzed quantitative relationships between gene silencing by the siRNA and ten parameters from published siRNA sequences. The four nonlinear significant parameters for designing siRNA are the RNA single-stranded index (SSi), a new parameter that identifies the target position and its related secondary structures, the GC content, /spl Delta/G free energy of the siRNA, and the 5'GC content of the first four bases of the antisense siRNA. The nonlinear complexity suggested that one should not use simple criteria such as a GC content of around 30 to 50% or the absence of the sequence pattern GGG for designing siRNA. Our results indicate that the targeted mRNA secondary structure is a statistically significant determinant in gene silencing and should be used to optimize RNAi technology.
Sponsorship	IEEE Comput. Soc. Tech. Committee on Computational Medicine Texas Tech Univ. College of Eng
Starting Page	335
Ending Page	342
File Size	298549
Page Count	8
File Format	PDF
ISBN	0769521045
ISSN	10637125
DOI	10.1109/CBMS.2004.1311737
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2004-06-25
Publisher Place	USA
Access Restriction	Subscribed
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	RNA Humans Throughput Genetics Functional analysis Cancer Genomics Bioinformatics Coagulation Reduced instruction set computing
Content Type	Text
Resource Type	Article
Subject	Radiology, Nuclear Medicine and Imaging Computer Science Applications

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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