| abstract |
A method for the preparation of an antisense oligonucleotidenor derivative thereof comprising the steps of selecting antarget nucleic acid coding for an expression product, ifnnecessary elucidating its sequencen generating the antisense oligonucleotide with thenproviso that the oligonucleotide comprises at least 8nbut not more than 30 residues of the nucleotides, the oligonucleotide comprises at maximum eight elements,ncapable of forming three hydrogen bonds each toncytosine bases, the oligo nucleotide does not contain four consecutivenelements, capable of forming three hydrogen bonds eachnwith four consecutive cytosine bases (N a CCCCN a ) withinnthe target molecule, wherein a = 0 - 20, the oligonucleotide does also not contain 2 series ofnthree consecutive elements, capable of forming threenhydrogen bonds each with three consecutive cytosinnbases (N a C b N a C b N a ) within the target molecule, whereinna = 0 - 20 and b = 3 - 8 and the ratio between residues forming two hydrogen bondsnper residue (2H-bond-R) with its target molecule andnthose residues forming three hydrogen bonds per residuen(3H-bond-R), is ruled by the following specifications:n 3H-bond-R 2H-bond-R = 0.33 - 072 n and synthesizing the oligonucleotide thusngenerated in a per se known manner. |