Compositions and Methods for TTR Gene Editing and Treating ATTR Amyloidosis Comprising a Corticosteroid or Use Thereof

A method of treating amyloidosis associated with TTR (ATTR), the method comprising administering to a human subject in need thereof (a) a first dose of a first corticosteroid, (b) a second dose of a second corticosteroid, and (c) a pharmaceutical formulation, wherein

• the first dose of the first corticosteroid is administered about 8 to 24 hours before the pharmaceutical formulation is administered;
• the second dose of the second corticosteroid is administered about 1 to 2 hours before the pharmaceutical formulation is administered;
• the first corticosteroid and/or the second corticosteroid is dexamethasone, betamethasone, prednisone, prednisolone, methylprednisolone, cortisone, hydrocortisone, triamcinolone, or ethamethasoneb;
• and
• the pharmaceutical formulation comprises
• (i) a single guide RNA (sgRNA) comprising the sequence mA*mA*mA*GGCUGCUGAUGACACCUGUUUUAGAmGmCmUmAmGmAmAmAmUmA mGmCAAGUUAAAAUAAGGCUAGUCCGUUAUCAmAmCmUmUmGmAmAmAmAmAm GmUmGmGmCmAmCmCmGmAmGmUmCmGmGmUmGmCmU*mU*mU*mU (SEQ ID NO:
• 87), wherein a * indicates a phosphorothioate (PS) linkage and a lower case “m” indicates that the nucleotide is 2′-O-Me modified and
• (ii) a messenger RNA (mRNA) comprising an open reading frame (ORF) that is at least 98% identical to SEQ ID NO:
• 311, wherein the ORF encodes a Cas9 and each thymidine in SEQ ID NO:
• 311 is replaced with a modified or unmodified uridine.