Muscle targeting complexes and uses thereof for treating dystrophinopathies
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 promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.
Claims21
1-72. (canceled)
A method comprising:
- (a) providing an anti-transferrin receptor antibody;
- (b) providing an oligonucleotide;
- and
- (c) covalently linking the anti-transferrin receptor antibody to a 5′ end of the oligonucleotide to form a complex, wherein the complex comprises the anti-transferrin receptor antibody covalently linked, via a protease-sensitive linker, to the oligonucleotide;
- wherein the anti-transferrin receptor antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and the light chain variable region comprise human or humanized framework regions, and 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 permits transferrin binding to TfR1;
- and
- wherein the oligonucleotide of the complex is 30 nucleotides in length, is a phosphorodiamidate morpholino oligomer (PMO), and comprises a region of complementarity that is fully complementary, along a length of 25, 26, 27, 28, 29, or 30 contiguous nucleotides, to the annealing site of an oligonucleotide consisting of the sequence of SEQ ID NO:
- 195.
Dependencies are inferred from the claim text.