Exosome gene therapy for treating inner ear disease
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsMei He, Xiaoshu Pan
Life of this patent
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Abstract
Provided herein are compositions and methods useful in the treatment of hearing loss diseases, such as by correction of mutations in genes associated with hearing.
Claims38
A method comprising providing to a subject a CRISPR-associated endonuclease, a guide RNA (gRNA), and a template nucleic acid, wherein the gRNA targets a MYO7A gene.
The method of any preceding claim, wherein the CRISPR-associated endonuclease is provided as a nucleic acid encoding a protein.
The method of any preceding claim, wherein the CRISPR-associated endonuclease and the gRNA are provided as a ribonucleoprotein (RNP) complex or a nucleic acid encoding an RNP complex.
The method of any preceding claim, wherein the template nucleic acid comprises a portion of a nucleic acid sequence encoding a wild-type MYO7A protein or a sequence capable of specifically binding to a portion of a nucleic acid sequence encoding a wild-type MYO7A protein.
The method of any preceding claim, wherein the gRNA comprises, consists essentially of, or consists of a nucleic acid sequence of 10-30 or 15-25 consecutive nucleotides of the sequence of NCBI Reference Sequence NM_001256081.1 (SEQ ID NO:
- 7), NM_001256082.1 (SEQ ID NO:
- 9), NM_001256083.1 (SEQ ID NO:
- 11), or NM_008663.2 (SEQ ID NO:
- 13), or a nucleotide sequence of 10-30 or 15-25 nucleotides capable of specifically hybridizing to an equal-length portion of the sequence of NCBI Reference Sequence NM_001256081.1 (SEQ ID NO:
- 7), NM_001256082.1 (SEQ ID NO:
- 9), NM_001256083.1 (SEQ ID NO:
- 11), or NM_008663.2 (SEQ ID NO:
- 13).
The method of any preceding claim, wherein the gRNA comprises, consists essentially of, or consists of a nucleic acid sequence of, or capable of specifically binding to any one of the sequences of
- (SEQ ID NO:
- 16)
- GATGACGTTCATAGGCCGGTTGG,
- (SEQ ID NO:
- 17)
- CTTGCTCTCCTCATCGATGAGGG,
- (SEQ ID NO:
- 18)
- ATGAGGGAGATGACGTTCATAGG,
- (SEQ ID NO:
- 19)
- AGGGAGATGACGTTCATAGGCGG,
- (SEQ ID NO:
- 20)
- CAATCATGTCCAGTGCTTCCTGG,
- (SEQ ID NO:
- 40)
- GAUGACGUUCAUAGGCGGGU,
- (SEQ ID NO:
- 41)
- GACGUUCAUAGGCGGGU,
- (SEQ ID NO:
- 42)
- AGGGAGAUGACGUUCAUAGG,
- (SEQ ID NO:
- 43)
- GAGAUGACGUUCAUAGG,
- (SEQ ID NO:
- 44)
- CUUGCUCUCCUCAUCGAUGA,
- or
- (SEQ ID NO:
- 45)
- AUGAGGGAGAUGACGUUCAU,
- wherein each uracil base (U) may independently and optionally be replaced with a thymine base (T) and each T may independently and optionally be replaced with a U.
The method of any preceding claim, wherein the CRISPR-associated endonuclease, the gRNA, and/or the template nucleic acid are encapsulated within an extracellular vesicle.
A composition comprising a CRISPR-associated endonuclease or a nucleic acid sequence encoding a CRISPR-associated endonuclease, a guide RNA (gRNA), and a template nucleic acid, wherein the gRNA is targets a MYO7A gene.
Dependencies are inferred from the claim text.