CPC C12N 15/113 (2013.01) [A61P 25/28 (2018.01); C12N 9/22 (2013.01); C12N 15/102 (2013.01); A61K 48/00 (2013.01); A61K 48/0091 (2013.01); C12N 15/111 (2013.01); C12N 2310/20 (2017.05); C12N 2310/321 (2013.01); C12N 2800/80 (2013.01)] | 21 Claims |
1. A method of treating amyloidosis associated with TTR (ATTR), comprising administering a composition to a subject in need thereof, wherein the composition comprises (i) an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent and (ii) a single guide RNA comprising in 5′ to 3′ order, 1) one of the following (a)-(c): a. a guide sequence comprising the sequence of SEQ ID NO: 23; b. a guide sequence that is at least 17, 18, or 19 contiguous nucleotides of the sequence of SEQ ID NO: 23; or c. a guide sequence that is at least 90% identical to the sequence of SEQ ID NO: 23, and (2) the sequence of SEQ ID NO: 125, wherein the sequence of SEQ ID NO: 125 comprises a modification pattern of nucleotides 21-100 of SEQ ID NO: 3 (GUUUUAGAmGmCmUmAmGmAmAmAmUmAmGmCAAGUUAAAAUAAGGCU AGUCCGUUAUCAmAmCmUmUmGmAmAmAmAmAmGmUmGmGmCmAmCmC mGmAmGmUmCmGmGmUmGmCmU*mU*mU*mU), thereby treating ATTR, wherein a * indicates a phosphorothioate (PS) linkage and a lower case “m” indicates that the nucleotide is 2′-O-Me modified.
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