Correlation Between Gene Silencing Activity and Structural Features of Antisense Oligodeoxynucleotides and Target RNA

Article type: Research Article

Authors: Liao, Li | Li, Zhongwei

Affiliations: Department of Computer and Information Sciences, University of Delaware, Newark, DE 19716, USA. E-mail: [email protected] | Department of Biomedical Sciences, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA

Abstract: Antisense oligonucleotides inactivate mRNA targets, providing a tool for post-transcriptional gene silencing and a potential novel treatment for many diseases. Reliable design of active antisense depends on better understanding of the mechanism of antisense-target RNA interaction. We have studied the correlation between activity of antisense oligodeoxynucleotides (ASO) and structural features of both antisense and target RNAs. A total of 348 ASOs with known activities and their target RNA sequences are classified into categories according to their predicted secondary structural features. Statistical analysis showed that higher activity is more likely to happen at RNA stem-loops than at other RNA structural categories. The data suggest a weak correlation between the stability of ASO structure and activity. Remarkably, a structural fit between ASO and target seems important for antisense activity. Significantly higher antisense activity is achieved with stem-loop ASOs on stem-loop or linear RNA targets.

Keywords: Antisense, RNA, gene inactivation, mRNA target, secondary structure, oligodeoxynucleotides, stem-loop, statistical analysis

Journal: In Silico Biology, vol. 7, no. 4-5, pp. 527-534, 2007