US 2026/0176631 A1 · Hepatic Delivery Platforms For Multimeric RNAi Agent Conjugates and Methods of Use Thereof

Abstract

The present disclosure relates to delivery platforms that specifically and efficiently direct multimeric RNAi agent payloads to hepatocytes in a subject, in vivo. The delivery platforms disclosed herein include metabolically stabilized N-Acetylgalactosamine (NAG or GalNAc) targeting ligands conjugated to two or more RNAi agents, to facilitate the delivery of the oligonucleotide-based payloads to cells, including to hepatocytes. Pharmaceutical compositions that include the metabolically stabilized multimeric RNAi agent conjugate delivery platform are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a hepatocyte is desirable.

Claims30

Dependent claims

An RNAi agent for inhibiting expression of one or more genes, comprising:

a. a first antisense strand, wherein the antisense sense strand comprises between 18 and 23 nucleotides, and
b. a second antisense strand, wherein the second antisense strand comprises between 18 and 23 nucleotides;
and
c. one or more sense strands, wherein the one or more sense strands comprise a nucleotide sequence that is at least partially complementary to the first antisense strand and the second antisense strand;
and
d. a metabolically stabilized carbohydrate ligand;
wherein the metabolically stabilized carbohydrate ligand is covalently bound to the one or more sense strands.

4 more elements

Dependencies are inferred from the claim text.

Hepatic Delivery Platforms For Multimeric RNAi Agent Conjugates and Methods of Use Thereof

Life of this patent

Hepatic Delivery Platforms For Multimeric RNAi Agent Conjugates and Methods of Use Thereof

Life of this patent

Abstract

Claims30