US 2023/0145795 A1 · OLIGONUCLEOTIDE COMPOSITIONS AND METHODS OF USE THEREOF

Abstract

Among other things, the present disclosure provides RHO oligonucleotides, compositions, and methods. In some embodiments, provided oligonucleotides comprise nucleobase modifications, sugar modifications, internucleotidic linkage modifications and/or patterns thereof, and have improved properties, activities and/or selectivities. In some embodiments, the present disclosure provides RHO oligonucleotides, compositions and methods for preventing and/or treating RHO-related conditions, disorders or diseases, such as retinopathy (e.g, retinal degeneration, retinal degenerative disease, retinal degenerative disorder, inherited retinal degenerative disorder, retinitis pigmentosa, autosomal dominant retinitis pigmentosa, etc.).

Claims31

Dependent claims

An oligonucleotide, wherein the oligonucleotide comprises a plurality of chiral internucleotidic linkages each of which independently comprises a stereodefined linkage phosphorus, wherein the pattern of backbone chiral centers of the oligonucleotide comprises [(Rp/Op)n(Sp)m]y, wherein:

n is 1-10;
m is 1-50;
y is 2-10;
Op indicates a linkage phosphorus being achiral;
Rp indicates a linkage phosphorus having R configuration;
Sp indicates a linkage phosphorus having S configuration;
at least one [(Rp/Op)n(Sp)m] comprises RpSpSp;
and
wherein:
the oligonucleotide comprises a natural phosphate linkage;
each modified internucleotidic linkage is independently a phosphorothioate internucleotidic linkage;
and
the base sequence of the oligonucleotide is or comprises a sequence that is 75% identical or complementary to a target sequence in a RHO gene or a transcript thereof.

10 more elements

Dependencies are inferred from the claim text.

Oligonucleotide compositions and methods of use thereof

Life of this patent

Oligonucleotide compositions and methods of use thereof

Life of this patent

Abstract

Claims31