Rational selection of antisense oligonucleotide sequences.

The purpose of this review is to identify rational selection procedures for the identification of optimal antisense oligonucleotide sequences. The review is firstly focused on how to find optimal hybridization sites, and secondly on how to select sequences that bind to structured RNA. The methods reviewed range from the more empirical testing of large numbers of mRNA complementary sequences to the more systematic techniques, i.e. RNase H mapping, use of combinatorial arrays and prediction of secondary structure of mRNA by computational methods. Structures that bind to structured RNA, i.e. aptastrucs and tethered oligonucleotide probes, and foldback triplex-forming oligonucleotides are also discussed. Relating to selection of antisense sequences by aid of computational analysis, valuable www addresses are given along with examples of folded structures of mRNA.