US 12,281,313 B2
Compositions and methods for delivering nucleic acids to cochlear and vestibular cells
Jeffrey R. Holt, Boston, MA (US); Yukako Asai, Boston, MA (US); Paola Andrea Solanes Vega, Lausanne (CH); and Bernard Schneider, Lausanne (CH)
Assigned to Children's Medical Center Corporation, Boston, MA (US)
Filed by Children's Medical Center Corporation, Boston, MA (US); and École Polytechnique Fédérale de Lausanne, Lausanne (CH)
Filed on Sep. 2, 2020, as Appl. No. 17/010,556.
Application 17/010,556 is a continuation of application No. PCT/US2019/020794, filed on Mar. 5, 2019.
Claims priority of provisional application 62/638,697, filed on Mar. 5, 2018.
Prior Publication US 2020/0392516 A1, Dec. 17, 2020
Int. Cl. C12N 15/64 (2006.01); A61P 27/16 (2006.01)
CPC C12N 15/64 (2013.01) [A61P 27/16 (2018.01)] 13 Claims
 
1. An AAV vector, wherein the vector comprises:
a polynucleotide encoding:
a capsid comprising amino acid sequence: TLAVPFK (SEQ ID NO: 27); and
a polypeptide selected from the group consisting of TMC1, TMC2, MYO7A, USH1C, CDH23, PCDH15, SANS, CIB2, USH2A, VLGR1, WHRN, CLRN1, PDZD7, KCNQ4, TMPRSS3, STRC, EYA4, harmonin-a, b, and c, OTOF, GPR98, MYO6, MYO15A, LOXHD1, POU3F4, EYA1, WFS1, ACTG1, TMIE, PJVK, SYNE4, and FAM65B; and
a promoter that directs expression of the polynucleotide encoding the polypeptide.
 
6. A method, comprising: administering the AAV vector of claim 1 to an inner ear of a subject having a recessive mutation in a gene selected from the group consisting of: TMC1, TMC2, MYO7A, USH1C, CDH23, PCDH15, SANS, CIB2, USH2A, VLGR1, WHRN, CLRN1, PDZD7, KCNQ4, TMPRSS3, STRC, EYA4, harmonin-a, harmonin-b, harmonin-c, OTOF, GPR98, MYO6, MYO15A, LOXHD1, POU3F4, EYA1, WFS1, ACTG1, TMIE, PJVK, SYNE4, and FAM65B, thereby forming an AAV vector-encoded transgene, wherein the AAV vector-encoded transgene is a wild-type form of the mutated gene in the subject,
thereby expressing the polypeptide in the inner ear.
 
13. A method of transducing an outer hair cell, an inner hair cell, a vestibular hair cell, a spiral ganglion, or a vestibular ganglion in a subject having a defective gene, the method comprising:
injecting the AAV vector of claim 1 into an inner ear of the subject, thereby forming an AAV vector-encoded transgene, wherein the AAV vector-encoded transgene is a wild-type form of the defective gene of the subject,
thereby expressing the polypeptide in the outer hair cell, the inner hair cell, the vestibular hair cell, the spiral ganglion, or the vestibular ganglion, wherein the defective gene comprises a recessive mutation.