A method for the preparation of an antisense oligonucleotide or derivative
thereof comprising the steps of: selecting a target nucleic acid, if
necessary elucidating its sequence; generating the antisense
oligonucleotide with the proviso that: the oligonucleotide comprises at
least 8 residues; the oligonucleotide comprises at maximum twelve
elements, which are capable of forming three hydrogen bonds each to
cytosine bases; the oligonucleotide does not contain four or more
consecutive elements, capable of forming three hydrogen bonds each with
four consecutive cytosine bases (CCCC) within the target molecule or
alternatively four or more consecutive elements of GGGG; the
oligonucleotide does also not contain 2 or more series of three
consecutive elements, capable of forming three hydrogen bonds each with
three consecutive cytosine bases (CCC) within the target molecule, or
alternatively 2 or more series of three consecutive elements of GGG; and
the ratio between residues forming two hydrogen bonds per residue
(2H-bond-R) with the target molecule and those residues forming three
hydrogen bonds per residue (3H-bond-R) with the target molecule, is ruled
by the following specifications: 3H-bond-R/3H-bond-R+2H-bond-R.gtoreq.0.2-
9; and synthesizing the oligonucleotide thus generated in a per se known
manner.
