| 摘要 |
Patent No. 599237 Disclosed is a double stranded nucleic acid molecule having structure (A) set forth below: (A) 5’ N1-(N)x - Z 3’ (antisense strand) 3’ Z’-N2-(N’)y –z” 5’ (sense strand) wherein each of N2, N and N’ is an unmodified or modified ribonucleotide, or an unconventional moiety; wherein each of (N)x and (N’)y is an oligonucleotide in which each consecutive N or N’ is joined to the adjacent N or N’ by a covalent bond; wherein each of x and y is independently an integer between 17 and 39; wherein the sequence of (N’)y has complementarity to the sequence of (N)x and the sequence of (N)x has complementarity to a consecutive sequence in a target RNA; wherein N1 is covalently bound to (N)x and forms a Watson-Crick base pair with N2; wherein N1 is not complementary to the corresponding nucleotide in the target RNA; wherein N1 is selected from the group consisting of natural or modified adenosine, and deoxyadenosine when the corresponding nucleotide in the target RNA sequence is adenosine; or N1 is selected from the group consisting of natural or modified adenosine, deoxyadenosine, deoxyuridine, deoxythymidine and ribothymidine when the corresponding nucleotide in the target RNA sequence is cytidine; or N1 is selected from the group consisting of natural or modified adenosine, deoxyadenosine, uridine, deoxyuridine, ribothymidine and deoxythymidine when the corresponding nucleotide in the target RNA sequence is guanosine; or N1 is selected from the group consisting of natural or modified uridine, deoxyuridine, ribothymidine and deoxythymidine when the corresponding nucleotide in the target RNA sequence is uridine; wherein z” may be present or absent, but if present is a capping moiety covalently attached at the 5’ terminus of N2- (N’)y; and wherein each of Z and Z’ is independently present or absent, but if present is independently 1-5 consecutive nucleotides, consecutive non-nucleotide moieties or a combination thereof covalently attached at the 3’ terminus of the strand in which it is present; or a pharmaceutically acceptable salt of the double stranded nucleic acid molecule. |
