Design of antisense oligonucleotides

Antisense oligonucleotides: from design to therapeutic application.

1. An antisense oligonucleotide (ASO) is a short strand of deoxyribonucleotide analogue that hybridizes with the complementary mRNA in a sequence-specific manner via Watson-Crick base pairing. Formation of the ASO-mRNA heteroduplex either triggers RNase H activity, leading to mRNA degradation, induces translational arrest by steric hindrance of ribosomal activity, interferes with mRNA maturatio...

Antisense oligonucleotides and the rational design of new antitumor drugs.

suming and resource-costly. For colon cancer, as for many other tumors, this goal is far from accomplished nowadays despite considerable effort. High costs should include, as a relevant issue, the high number of agents to be assessed and then discarded along the various stages of selection. To render this search more efficient, both official agencies and private ventures tend to rationalize thi...

Concepts to automate the theoretical design of effective antisense oligonucleotides

Among the large number of possible antisense species against a given target RNA, only a small number shows effective suppression of the target gene in living cells. In the case of short-chain antisense oligonucleotides (asON) which usually comprise less than approximately 25 nucleotides, local structures of the target RNA seem to be of particular importance for the extent of gene suppression. E...

Design of antisense oligonucleotides stabilized by locked nucleic acids.

The design of antisense oligonucleotides containing locked nucleic acids (LNA) was optimized and compared to intensively studied DNA oligonucleotides, phosphorothioates and 2'-O-methyl gapmers. In contradiction to the literature, a stretch of seven or eight DNA monomers in the center of a chimeric DNA/LNA oligonucleotide is necessary for full activation of RNase H to cleave the target RNA. For ...

Design, Synthesis, and Biochemical Evaluation of Modified Antisense Oligonucleotides