Materials and methods for treatment of friedreich ataxia and other related disorders
AssigneeCrispr Therapeutics AG
InventorsAnte Sven Lundberg, Samarth Kulkarni, Lawrence Klein, Hari Kumar Padmanabhan
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Abstract
The present application provides materials and methods for treating a patient with one or more condition associated with FXN whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of FXN gene in a cell by genome editing.
Claims55
A method for editing a Frataxin (FXN) gene in a cell by genome editing comprising:
- introducing into the cell one or more deoxyribonucleic acid (DNA) endonucleases to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near the FXN gene that results in permanent deletion of the expanded trinucleotide repeat or replacement of one or more nucleotide bases, or one or more exons and/or introns within or near the FXN gene, thereby restoring the FXN gene function.
A method for editing a Frataxin (FXN) gene in a cell by genome editing comprising:
- introducing into the cell one or more deoxyribonucleic acid (DNA) endonucleases to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near the FXN gene or FXN regulatory elements that results in one or more permanent insertion, deletion or mutation of at least one nucleotide within or near the FXN gene, thereby reducing or eliminating the expression or function of aberrant FXN gene products.
An ex vivo method for treating a patient having a FXN related condition or disorder comprising:
- (a) creating a patient specific induced pluripotent stem cell (iPSC);
- (b) editing within or near a Frataxin (FXN) gene or other DNA sequences that encode regulatory elements of the FXN gene of the iPSC;
- (c) differentiating the genome-edited iPSC into a neuron or glial cell of the Central Nervous System (CNS);
- and
- (d) implanting said neuron or glial cell of the Central Nervous System (CNS) into the patient.
An ex vivo method for treating a patient having a FXN related condition or disorder comprising:
- (a) isolating a mesenchymal stem cell from the patient;
- (b) editing within or near a Frataxin (FXN) gene or other DNA sequences that encode regulatory elements of the FXN gene of the mesenchymal stem cell;
- (c) differentiating the genome-edited mesenchymal stem cell into a neuron or glial cell of the Central Nervous System (CNS);
- and
- (d) implanting the neuron or glial cell of the Central Nervous System (CNS) into the patient.
An in vivo method for treating a patient with a FXN related disorder comprising:
- editing the Frataxin (FXN) gene in a cell of the patient.
A method of altering the contiguous genomic sequence of a FXN gene in a cell comprising:
- contacting said cell with one or more deoxyribonucleic acid (DNA) endonuclease to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs).
A single-molecule guide RNA comprising:
- at least a spacer sequence that is an RNA sequence corresponding to any of SEQ ID NOs:
- 5305-37514 and 37549.
Dependencies are inferred from the claim text.