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US 2023/0407315 A1Published application
Compositions and methods for treating non-age-associated hearing impairment in a human subject
AssigneeAkouos, Inc.
InventorsEmmanuel John Simons, Ellen Reisinger, Sebastian Kügler, Hanan Al-Moyed
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Abstract
Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.
Claims37
A composition comprising two different nucleic acid vectors, wherein:
- each of the two different vectors comprises a coding sequence that encodes a different portion of an otoferlin protein, each of the encoded portions being at least 30 amino acid residues in length;
- no single vector of the at least two different vectors encodes a full-length otoferlin protein;
- a first of the two different vectors comprises a promoter operably linked to a coding sequence that encodes an N-terminal portion of the otoferlin protein;
- at least one of the coding sequences comprises a nucleotide sequence spanning two neighboring exons of otoferlin genomic DNA, and lacks an intronic sequence between the two neighboring exons;
- and
- when introduced into a mammalian cell the at least two different vectors undergo concatemerization or homologous recombination with each other, thereby forming a recombined nucleic acid that encodes a full-length otoferlin protein.
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A composition comprising two different nucleic acid vectors, wherein:
- a first nucleic acid vector of the two different nucleic acid vectors comprises a promoter, a first coding sequence that encodes an N-terminal portion of an otoferlin protein positioned 3′ of the promoter, and a splicing donor signal sequence positioned at the 3′ end of the first coding sequence;
- and
- a second nucleic acid vector of the two different nucleic acid vectors comprises a splicing acceptor signal sequence, a second coding sequence that encodes a C-terminal portion of an otoferlin protein positioned at the 3′ end of the splicing acceptor signal sequence, and a polyadenylation sequence at the 3′ end of the second coding sequence;
- wherein each of the encoded portions is at least 30 amino acid residues in length,
- wherein the amino acid sequences of the encoded portions do not overlap,
- wherein no single vector of the two different vectors encodes a full-length otoferlin protein, and,
- when the coding sequences are transcribed in a mammalian cell, to produce RNA transcripts, splicing occurs between the splicing donor signal sequence on one transcript and the splicing acceptor signal sequence on the other transcript, thereby forming a recombined RNA molecule that encodes a full-length otoferlin protein.
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Dependencies are inferred from the claim text.