Cationic siRNAs, synthesis and use for RNA interference

摘要

Disclosed is a cationic siRNA, comprising a fragment of double-stranded RNA at the ends of which are grafted oligocations, the number of grafted cationic charges being greater than that of the anionic charges borne by the internucleoside phosphates of the RNA strands. Further disclosed is a process for the automated synthesis of a strand of cationic siRNA comprising: (i) sequentially coupling from 3' to 5', 15 to 30 ribonucleotides to a solid support, preceded and/or followed by the sequential coupling of cationic synthons, the strand comprising formula (VI): dT-dT-(N)i-Aj or Aj-dT-dT-(N)i wherein (N)i represents an i-mer oligoribonucleotide, with i=15 to 30 or i=19 to 30, and any chemical modifications or substitutions that conserve the A form of the double helix of the siRNA, Aj represents a j-mer oligocation, with j= 20 to 30, A as defined within the specification (ii) deprotecting the tert-butyldimethylsilyl protecting group in the 2'-OH position.