Methods and compositions for treatment of myotonic dystrophy

A chimeric polypeptide comprising:

• (i) a functional fragment of an MBNL1 polypeptide, and (ii) a targeting moiety, wherein the targeting moiety comprises an antibody or antigen-binding fragment, wherein the targeting moiety transits cellular membranes via an equilibrative nucleoside transporter 2 (ENT2) transporter;
• and wherein the chimeric polypeptide is capable of binding CUG repeats.

A nucleic acid construct, comprising a nucleotide sequence that encodes a functional fragment of an MBNL1 polypeptide, operably linked to a nucleotide sequence that encodes a targeting moiety, wherein the targeting moiety comprises an antibody or antigen-binding fragment, wherein the targeting moiety transits cellular membranes via an equilibrative nucleoside transporter 2 (ENT2) transporter;

• wherein the nucleic acid construct encodes a chimeric polypeptide having MBNL biological activity and having the targeting activity of the targeting moiety;
• and wherein the chimeric polypeptide is capable of binding CUG repeats.

A method of delivering a chimeric polypeptide into a cell, comprising contacting a cell with a chimeric polypeptide, which chimeric polypeptide comprises:

• (i) a functional fragment of an MBNL1 polypeptide and (ii) a targeting moiety, wherein the targeting moiety comprises an antibody or antigen-binding fragment, wherein the targeting moiety transits cellular membranes via an equilibrative nucleoside transporter 2 (ENT2) transporter;
• and wherein the chimeric polypeptide is capable of binding CUG repeats.