Modified sina molecules, methods and uses thereof

Abstract

The present disclosure relates to a double stranded short interfering nucleic acid (siNA) agent for use in medicine, in particular for use in the treatment of ophthalmic diseases comprising an antisense ribonucleotide sequence arranged to base-pair to a substantially complementary sense ribonucleotide sequence; wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a 2′-O-methyl modification or a 2′-fluoro modification; wherein both the sense strand and the antisense strand independently comprise at least one phosphorothioate internucleotide linkage; wherein the antisense ribonucleotide sequence is substantially complementary to a sense ribonucleotide sequence except in up to 6 nucleotides; wherein the sense strand comprises 15 to 21 nucleotides; wherein each nucleotide or each of the first 18 contiguous nucleotides in the 5′-3′ direction comprise a modification that is different from the modification of the adjacent nucleotide; and wherein the first modification in the antisense strand is a 2′-O-methyl modification.

Dependencies are inferred from the claim text.