Compositions and methods for treating CEP290 associated disease
AssigneeEditas Medicine, Inc.
InventorsMorgan Lee Maeder, Rina J. Mepani, Michael Stefanidakis
Life of this patent
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Abstract
Nucleic acids and viral vectors, particularly adeno-associated virus (AAV) vectors are provided that encode Cas9 and paired guide RNAs. The nucleic acids and vectors, and compositions that comprise them, can be used in methods to treat subjects, to alter cells in subjects who may suffer from an inherited retinal dystrophy such as CEP290 associated disease or who may be in need of alteration of a cell or a cellular nucleic acid sequence associated with an inherited retinal dystrophy such as the CEP290 gene, and/or to treat inherited retinal dystrophies including CEP290 associated disease.
Claims22
A method of treating a subject, comprising:
- contacting a retina of the subject with one or more recombinant viral vectors comprising one or more nucleic acids encoding a Cas9, a first guide RNA (gRNA) and a second gRNA,
- wherein (a) the first and second gRNAs are adapted to form first and second ribonucleoprotein complexes with the Cas9, and (b) the first and second ribonucleoprotein complexes are adapted to cleave first and second cellular nucleic acid sequences on first and second sides of a CEP290 target position, thereby altering a nucleotide sequence of the CEP290 target position,
- wherein the first cellular nucleic acid sequence is different from the second cellular nucleic acid sequence,
- wherein the one or more recombinant viral vectors comprise a promoter selected from the group consisting of:
- a CMV promoter sequence having at least 90% sequence identity to SEQ ID NO:
- 13,
- an EFS promoter sequence having at least 90% sequence identity to SEQ ID NO:
- 14, or
- an hGRK promoter sequence having at least 90% sequence identity to SEQ ID NO:
- 15;
- and
- wherein the one or more recombinant viral vectors contact the retina at a dose of 1×1011 viral genomes (vg)/mL to 9×1013 vg/mL.
A method of altering a retinal cell, comprising:
- contacting a retina of a subject with one or more recombinant viral vectors comprising one or more nucleic acids encoding a Cas9, a first gRNA and a second gRNA, wherein the first gRNA comprises a targeting domain selected from the group consisting of SEQ ID NOS:
- 1-3 and the second gRNA comprises a targeting domain selected from the group consisting of SEQ ID NOS:
- 4-6,
- wherein the one or more recombinant viral vectors comprise a promoter selected from the group consisting of:
- a CMV promoter sequence having at least 90% sequence identity to SEQ ID NO:
- 13,
- an EFS promoter sequence having at least 90% sequence identity to SEQ ID NO:
- 14, or
- an hGRK promoter sequence having at least 90% sequence identity to SEQ ID NO:
- 15;
- and
- wherein the one or more recombinant viral vectors contact the retina at a dose of 1×1011 vg/mL to 9×1013 vg/mL.
A method of treating a subject having an inherited retinal dystrophy, comprising:
- administering to a retina of the subject with one or more recombinant viral vectors comprising one or more nucleic acids encoding a Cas9 and a first gRNA comprising a sequence having at least 90% sequence identity to a sequence selected from SEQ ID NOS:
- 7 and 8;
- wherein (a) the first gRNA is adapted to form a first ribonucleoprotein complex with the Cas9, and (b) the first ribonucleoprotein complex is adapted to cleave a first cellular nucleic acid sequence associated with the inherited retinal dystrophy, thereby altering the first cellular nucleic acid sequence,
- wherein the one or more recombinant viral vectors comprise a promoter selected from the group consisting of:
- a CMV promoter sequence having at least 90% sequence identity to SEQ ID NO:
- 13,
- an EFS promoter sequence having at least 90% sequence identity to SEQ ID NO:
- 14, or
- an hGRK promoter sequence having at least 90% sequence identity to SEQ ID NO:
- 15;
- and
- wherein the one or more recombinant viral vectors are administered to the retina at a dose of 1×1011 vg/mL to 9×1013 vg/mL.
Dependencies are inferred from the claim text.