Insertion of anti-tfr:gaa and anti-cd63:gaa for the treatment of Pompe disease.

Abstract

Nucleic acid constructs and compositions are also provided that allow the insertion of a coding sequence of a multidomain therapeutic protein (e.g., the GAA fusion protein) into a target genomic locus, such as an endogenous ALB locus, and / or the expression of the coding sequence of the multidomain therapeutic protein (e.g., the GAA fusion protein).Nucleic acid constructs and compositions can be used in methods of integrating a multidomain therapeutic protein (e.g., GAA fusion protein) into a target genomic locus, methods of expressing a multidomain therapeutic protein (e.g., GAA fusion protein) in a cell, methods of reducing glycogen accumulation, methods of treating Pompe disease or GAA deficiency in a subject, and methods of preventing or reducing the occurrence of signs or symptoms of Pompe disease in a subject, including neonatal cells and subjects.