Double-stranded oligonucleotides inhibiting C3 gene expression, conjugates and uses thereof

Abstract

Relates to the field of medicines, in particular to a double-stranded oligonucleotide for inhibiting C3 gene expression, a conjugate and application thereof. The double-stranded oligonucleotide or the conjugate thereof can obviously inhibit the expression of C3 mRNA in HepG2 cells; c3 mRNA expression in an animal body can be obviously inhibited; the C3 protein level in cynomolgus monkey serum can be obviously reduced, and the inhibition effect can last to the 42nd day; the complement substitution pathway of cynomolgus monkey serum can be obviously inhibited, but the classical pathway of serum complement is not influenced; c3 mRNA (messenger ribonucleic acid) and protein level of a CFA-IgA mouse can be reduced; c3 deposition in the kidney tissue can be reduced, and the disease course of a patient with C3 deposition in the kidney tissue can be improved; and animal hematology and blood biochemistry are not obviously abnormal. The double-stranded oligonucleotides or conjugates thereof contribute to the alleviation, prevention and / or treatment of diseases or conditions mediated by the C3 gene.

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