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.