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AssigneeTune Therapeutics, Inc.
InventorsMatthew P. GEMBERLING, Jennifer KWON, Matthew WOLPERT, Charles A. GERSBACH, Kendra CONGDON, Dilara SEN
Estimating the term…
Provided in some aspects are compositions, such as DNA-targeting systems, fusion proteins, guide RNAs (gRNAs), and pluralities and combinations thereof, that bind to or target a frataxin (FXN) locus. In particular, the present disclosure relates to the modulation of expression of the FXN gene. In some aspects, the present disclosure also relates to poly nucleotides, vectors, cells and pluralities and combinations thereof, that encode or comprise the DNA-targeting systems, fusion proteins, gRNAs or pluralities or combinations thereof, and methods and uses related to the provided compositions, for example, in modulating the expression of FXN, and/or in the treatment or therapy of diseases or disorders that involve the activity, function or expression of FXN, such as Friedreich's Ataxia (FA).
A DNA-targeting system comprising:
A DNA-targeting system comprising a DNA-targeting domain that binds to a target site in an enhancer of a frataxin (FXN) locus.
A DNA-targeting system comprising:
A DNA-targeting system comprising a DNA-targeting domain that is a Cas-guide RNA (gRNA) combination comprising:
A DNA-targeting system comprising a DNA-targeting domain that is a Cas-guide RNA (gRNA) combination comprising:
A DNA-targeting system comprising a DNA-targeting domain that is a Cas-guide RNA (gRNA) combination comprising:
A DNA-targeting system comprising a DNA-targeting domain that is a Cas-guide RNA (gRNA) combination comprising:
A DNA-targeting system comprising:
A DNA-targeting system comprising a DNA-targeting domain that is a Cas-guide RNA (gRNA) combination comprising:
A DNA-targeting system comprising a DNA-targeting domain that is a Cas-guide RNA (gRNA) combination comprising:
A DNA-targeting system comprising a DNA-targeting domain that is a Cas-guide RNA (gRNA) combination comprising:
A guide RNA (gRNA) that binds a target site in an enhancer region of a frataxin (FXN) locus, wherein the target site is located within the genomic coordinates human genome assembly GRCh38 (hg38) chr9:69,027,282-69,028,497.
A guide RNA (gRNA) that binds a target site in a regulatory DNA element of a frataxin (FXN) locus wherein:
A guide RNA (gRNA) that binds a target site in a regulatory DNA element of a frataxin (FXN) locus wherein:
A combination, comprising:
A combination, comprising:
A fusion protein comprising (1) a DNA-targeting domain or a component thereof and (2) at least one effector domain, wherein:
A fusion protein comprising (1) a Cas protein or a variant thereof and (2) at least one effector domain, wherein the effector domain increases transcription of a FXN locus.
A fusion protein comprising (1) a first polypeptide of a split variant Cas protein comprising an N-terminal fragment of a Cas protein and an N-terminal Intein, and (2) at least one effector domain, wherein the effector domain increases transcription of a FXN locus.
A fusion protein comprising (1) a second polypeptide of a split variant Cas protein comprising a C-terminal fragment of a Cas protein and a C-terminal Intein and (2) at least one effector domain, wherein the effector domain increases transcription of the FXN locus.
A fusion protein comprising (1) a Staphylococcus aureus dCas9 protein (dSaCas9) and (2) at least one effector domain, wherein the effector domain increases transcription of a frataxin (FXN) locus.
A combination comprising the fusion protein of any of claims 83-111 and at least one gRNA, optionally wherein the at least one gRNA is a gRNA of any of claims 118-151.
Dependencies are inferred from the claim text.