B4GALT1 Variants And Uses Thereof

A method of treating a subject who is not a carrier of a B4GALT1 variant and has or is susceptible to developing a cardiovascular condition, comprising introducing into the subject:

• a) a Cas protein or a nucleic acid encoding the Cas protein;
• b) a guide RNA or a nucleic acid encoding the guide RNA, wherein the guide RNA forms a complex with the Cas protein and hybridizes to a guide RNA recognition sequence within an endogenous B4GALT1 gene, wherein the guide RNA recognition sequence includes or is proximate to a position corresponding to positions 53575 to 53577 of SEQ ID NO:1;
• and
• c) an exogenous donor sequence comprising a 5′ homology arm that hybridizes to a target sequence 5′ of the positions corresponding to positions 53575 to 53577 of SEQ ID NO:1, a 3′ homology arm that hybridizes to a target sequence 3′ of the positions corresponding to positions 53575 to 53577 of SEQ ID NO:1, and a nucleic acid insert comprising a nucleotide sequence encoding a serine at positions corresponding to positions 53575 to 53577 of SEQ ID NO:2 flanked by the 5′ homology arm and the 3′ homology arm,
• wherein the Cas protein cleaves the endogenous B4GALT1 gene in a cell in the subject and the exogenous donor sequence recombines with the endogenous B4GALT1 gene in the cell, wherein upon recombination of the exogenous donor sequence with the endogenous B4GALT1 gene, the serine is inserted at nucleotides corresponding to positions 53575 to 53577 of SEQ ID NO:1.

A method of treating a subject who is not a carrier of the B4GALT1 variant and has or is susceptible to developing a cardiovascular condition, comprising introducing into the subject:

• a) a Cas protein or a nucleic acid encoding the Cas protein;
• b) a guide RNA or a nucleic acid encoding the guide RNA, wherein the guide RNA forms a complex with the Cas protein and hybridizes to a guide RNA recognition sequence within an endogenous B4GALT1 gene, wherein the guide RNA recognition sequence comprises the start codon for the endogenous B4GALT1 gene or is within about 1,000 nucleotides of the start codon or is selected from SEQ ID NOS:9-12;
• and
• c) an expression vector comprising a recombinant B4GALT1 gene comprising a nucleotide sequence encoding a serine at positions corresponding to positions 53575 to 53577 of SEQ ID NO:2, wherein the Cas protein cleaves or alters expression of the endogenous B4GALT1 gene in a cell in the subject and the expression vector expresses the recombinant B4GALT1 gene in the cell in the subject.