CATIONIC siRNA, SYNTHESIS AND APPLICATION IN RNA INTERFERENCE

摘要

1. Cationic siRNAs, characterized in that they are fragments of double-stranded RNA, at the ends of which oligocations are grafted, and the total number of grafted cationic charges is comparable to or exceeds the number of anionic charges of internucleoside phosphates of RNA chains. ! 2. Cationic siRNA according to claim 1, characterized in that the total amount of chemically grafted cationic charges, subtracted from the total amount of anionic charges of internucleoside phosphate groups, is from -30 to +50. ! 3. Cationic siRNA no 1 or 2, characterized in that in the double helix the complementarity of the chains is complete or partial. ! 4. The cationic siRNA according to claim 1, characterized in that each oligoribonucleotide has a simple chain extension at position 3 'of the double helix. ! 5. Cationic siRNA according to claim 1, characterized in that the oligocations are grafted at position 3 ′ and / or 5 ′ of the sense strand and / or at position 3 ′ of the antisense strand. ! 6. The cationic siRNA according to claim 1, characterized in that said fragments consist of double-stranded RNAs from 15 to 30 oligonucleotides long, in particular from 19 to 30 nucleotides, at the ends of which 1-3 oligocations are covalently bonded, the total number of cationic charges which is comparable to or exceeds the number of anionic charges of RNA. ! 7. Cationic siRNA according to claim 1, characterized in that at least one chain corresponds to the formula (I)! ! in which Ni denotes an i-dimensional oligoribonucleotide, where i = from 15 to 30, in particular from 19 to 30, as well as all chemical modifications or substitutions that preserve the siRNA double helix form A,! Aj denotes the j-dimensional oligocation, where j = 1-50, A corresponds! formula (II)! ! where R1, R2 and R3, the same or different, represent lower alkylene, with �