Chemically modified guide RNAs for genome editing with Cas12b

A chemically modified single guide RNA for a Cas12b protein, comprising:

• (i) a spacer sequence complimentary to a polynucleotide sequence located on a strand of a human ANGPTL3 gene, and wherein the spacer sequence is designed to hybridize to the polynucleotide sequence located on the human ANGPTL3 gene, and
• (ii) a scaffold sequence that serves as a binding scaffold for the Cas12b protein,
• wherein the spacer sequence comprises about 10 to about 40 nucleotides in length,
• wherein the scaffold sequence has a nucleotide base sequence, wherein the nucleotide base sequence has at least 90% identity to positions 1 to 97 of SEQ ID NO:
• 1,
• wherein the scaffold sequence comprises a plurality of different chemical modifications,
• wherein the plurality of different chemical modifications are at two or more nucleotide positions selected from positions 1-7, 11, 16-21, 25-31, 39, 42, 45-52, 57-62, 64, 65, and 70-87 as numbered in SEQ ID NO:
• 1 or a corresponding position or combination of corresponding positions thereof, and
• wherein the one or more chemical modifications comprise a 2′-O-methyladenosine, a 2′-O-methylcytidine, a 2′-O-methylguanosine, a 2′-O-methyluridine, a nebularine, a 2′-O-methylnebularine, or a phosphorothioate linkage.