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 rev iew is firstly focused on how to find optimal hybridization sites, and seco ndly on how to select sequences that bind to structured RNA. The methods re viewed range from the more empirical testing of large numbers of mRNA compl ementary 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. apta strucs and tethered oligonucleotide probes, and foldback tripler-forming ol igonucleotides are also discussed. Relating to selection of antisense seque nces by aid of computational analysis, valuable www addresses are given alo ng with examples of folded structures of mRNA. (C) 2000 Elsevier Science BN . All rights reserved.