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.
[1]
Dalia Cohen,et al.
Functional genomics to new drug targets
,
2004,
Nature Reviews Drug Discovery.
[2]
Gunther Hartmann,et al.
Antisense therapy in oncology: new hope for an old idea?
,
2001,
The Lancet.
[3]
A. Branch,et al.
A good antisense molecule is hard to find
,
1998
.
[4]
S. Freier,et al.
Effects of RNA secondary structure on cellular antisense activity.
,
2000,
Nucleic acids research.
[5]
E. Wagner,et al.
The effect of loop size in antisense and target RNAs on the efficiency of antisense RNA control.
,
1992,
Nucleic acids research.