Supplementation of liver enzyme expression

A method for supplementing liver enzyme expression in a subject in need thereof, comprising administering to the subject:

• a) an endonuclease having the amino acid sequence of SEQ ID NO:
• 54;
• b) an engineered guide polynucleotide capable of i) forming a complex with the endonuclease and ii) hybridizing to a target nucleic acid sequence within intron 1 of an albumin gene;
• and
• c) a donor template polynucleotide comprising a nucleic acid encoding a Factor VIII (FVIII) gene or a functional fragment thereof, thereby supplementing liver enzyme expression of Factor VIII in said subject, the nucleic acid having at least 98% sequence identity to any one of SEQ ID NOs:
• 12, 13, 16-23, 32, 33, or 56-59.