Method of reducing expression of DUX4 in a muscle cell by administering an anti-transferrin receptor antibody linked to an oligonucleotide targeting DUX4
AssigneeDyne Therapeutics, Inc.
InventorsRomesh R. Subramanian, Mohammed T. Qatanani, Timothy Weeden
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Abstract
Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.
Claims21
A method of reducing expression level of DUX4 in a muscle cell of a subject, the method comprising administering to the subject a complex that comprises an anti-transferrin receptor antibody covalently linked to an oligonucleotide that targets a DUX4 RNA,
- wherein the anti-transferrin receptor antibody binds in the range of C89 to F760 of human transferrin receptor protein 1 (TfR1) having an amino acid sequence as set forth in SEQ ID NO:
- 1 and wherein the anti-transferrin receptor antibody does not specifically bind to the transferrin binding site of TfR1;
- wherein the oligonucleotide is a single stranded oligonucleotide in the range of 15-35 nucleotides in length, wherein the oligonucleotide comprises a region of complementarity to the nucleotide sequence as set forth in SEQ ID NO:
- 46, wherein the region of complementarity is at least 15 nucleotides in length, and wherein the oligonucleotide is a phosphorodiamidate morpholino oligomer;
- and
- wherein the complex is administered to the subject by infusion and the oligonucleotide brings about reduction of expression level of DUX4 in the muscle cell.
Dependencies are inferred from the claim text.