RNA TARGETING OF MUTATIONS VIA SUPPESSOR tRNAs AND DEAMINASES
AssigneeThe Regents of the University of California
InventorsPrashant Mali, Dhruva Katrekar
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Abstract
Aspects of the disclosure relate to a gene therapy approach for diseases, disorders, or conditions caused by mutation in the stop codon utilizing modified tRNA. At least 10-15% of all genetic diseases, including muscular dystrophy (e.g. Duchene muscular dystrophy), some cancers, beta thalassemia, Hurler syndrome, and cystic fibrosis, fall into this category. Not to be bound by theory, it is believed that this approach is safer than CRISPR approaches due to minimal off-target effects and the lack of genome level changes.
Claims30
A method of treating or preventing an inherited disease in a subject, the method comprising:
- editing a target sequence of an RNA in a cell by administering to the subject a polynucleotide encoding a guide RNA, wherein the guide RNA comprises at least one of:
- (a) a sequence;
- (b) a structure;
- or
- (c) a combination of (a) and (b),
- that recruits an Adenosine Deaminase Acting on RNA (ADAR) in the cell, and wherein the guide RNA comprises at least one mismatch relative to the target sequence.
A method for treating a disease or disorder characterized by the presence of a point mutation in a target sequence of an RNA encoding a protein associated with the disease or disorder in a subject in need thereof, comprising:
- administering a polynucleotide encoding a guide RNA to the subject, wherein the guide RNA comprises a targeting domain that binds to the target sequence, and wherein an Adenosine Deaminase Acting on RNA (ADAR) edits an adenosine (A) of the target sequence to inosine (I).
A method for at least partially restoring expression of a protein, comprising:
- administering a polynucleotide encoding a guide RNA to a subject in need thereof, wherein the guide RNA comprises a targeting domain that binds to a target sequence of an RNA,
- wherein the RNA encodes the protein and wherein the target sequence comprises a point mutation,
- wherein an ADAR edits an adenosine (A) of the target sequence to inosine (I).
Dependencies are inferred from the claim text.