Small interfering RNA targeting C3 and uses thereof
This disclosure relates to isolated oligonucleotides comprising duplex regions targeting human complement C3 mRNA, and delivery systems, kits and compositions comprising the same, and methods of using the same for inhibiting or downregulating C3 gene expression.
1 . An isolated oligonucleotide comprising:
an antisense strand comprising the nucleic acid sequence 5′
[mUs][fUs][fA][mG][fU][mA][fG][mA][mA][fU][mU][mU][mC][fU][mC][fU][mG][mU][mA][mGs][mGs][mC] 3′ (SEQ ID NO: 451), and
a sense strand comprising the nucleic acid sequence 5′
[mCs][mUs][mA][mC][mA][fG][mA][fG][fA][fA][fA][mU][mU][mC][mU][mA][mC][mUs][mAs][mA][G1b][G1b][G1b] 3′ (SEQ ID NO: 444),
wherein “m” is a 2′-O-methyl modification, “f” is a 2′-F modification, “s” is a phosphorothioate internucleotide linkage, and “G1b” is a GalNAc G1b moiety.
2 . A delivery system comprising the isolated oligonucleotide of claim 1 , wherein the delivery system is a liposome, a nanoparticle, a polymer-based delivery system, a ligand-conjugate delivery system, or a combination thereof.
3 . A pharmaceutical composition comprising the isolated oligonucleotide of claim 1 , and a pharmaceutically acceptable carrier, diluent or excipient.
4 . An isolated oligonucleotide comprising an antisense strand and a sense strand:
the antisense strand consisting of the nucleic acid sequence 5′ [mUs][fUs][fA][mG][fU][mA][fG][mA][mA][fU][mU][mU][mC][fU][mC][fU][mG][mU][mA][mGs][mGs][mC] 3′ (SEQ ID NO: 451), and
the sense strand consisting of the nucleic acid sequence 5′
[mCs][mUs][mA][mC][mA][fG][mA][fG][fA][fA][fA][mU][mU][mC][mU][mA][mC][mUs][mAs][mA][G1b][G1b][G1b] 3′ (SEQ ID NO: 444),
wherein “m” is a 2′-O-methyl modification, “f” is a 2′-F modification, “s” is a phosphorothioate internucleotide linkage, and “G1b” is a GalNAc G1b moiety.
5 . A delivery system comprising the isolated oligonucleotide of claim 4 , wherein the delivery system is a liposome, a nanoparticle, a polymer-based delivery system, a ligand-conjugate delivery system, or a combination thereof.
6 . A pharmaceutical composition comprising the isolated oligonucleotide of claim 4 , and a pharmaceutically acceptable carrier, diluent or excipient.
7 . An isolated oligonucleotide consisting of an antisense strand and a sense strand:
the antisense strand consisting of the nucleic acid sequence 5′
[mUs][fUs][fA][mG][fU][mA][fG][mA][mA][fU][mU][mU][mC][fU][mC][fU][mG][mU][mA][mGs][mGs][mC] 3′ (SEQ ID NO: 451), and
the sense strand consisting of the nucleic acid sequence 5′
[mCs][mUs][mA][mC][mA][fG][mA][fG][fA][fA][fA][mU][mU][mC][mU][mA][mC][mUs][mAs][mA][G1b][G1b][G1b] 3′ (SEQ ID NO: 444),
wherein “m” is a 2′-O-methyl modification, “f” is a 2′-F modification, “s” is a phosphorothioate internucleotide linkage, and “G1b” is a GalNAc G1b moiety.
8 . A delivery system comprising the isolated oligonucleotide of claim 7 , wherein the delivery system is a liposome, a nanoparticle, a polymer-based delivery system, a ligand-conjugate delivery system, or a combination thereof.
9 . A pharmaceutical composition comprising the isolated oligonucleotide of claim 7 , and a pharmaceutically acceptable carrier, diluent or excipient.