Abstract: Compositions and methods for expressing alpha 1 antitrypsin (AAT) in a host cell are provided. Also provided are compositions and methods for treating subjects having alpha 1 antitrypsin deficiency (AATD).

Abstract: Compositions and methods for inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a neonatal cell, a population of neonatal cells, or a neonatal subject or for expressing a nucleic acid encoding a polypeptide of interest in a neonatal cell, a population of neonatal cells, or a neonatal subject are provided. Also provided are neonatal cells or populations of neonatal cells comprising a nucleic acid construct comprising a coding sequence for a polypeptide of interest inserted into a target genomic locus.

Abstract: The present disclosure relates to inhibitors of DNA protein kinase, and compositions and methods of use thereof. In some embodiments, the inhibitors have the structure of Formula I: or a salt thereof, wherein: x1 is C—R3 or N; R1 is C1-C3 alkyl; R2 is cycloalkyl or heterocyclyl, and cycloalkyl and heterocyclyl are optionally substituted with one or more R6; R3 is H or C1-C3 alkyl; R4 is H or C1-C3 alkyl; R5 is C1-C3 alkyl; each R6 is independently selected from hydroxy, halo, alkyl, alkoxy, cycloalkyl, amino, and cyano, or two R6, taken together with the atom or atoms to which they are bonded, form a spirocyclic or fused ring; and R7 is H or C1-C3 alkyl.

Abstract: Nucleic acid constructs and compositions that allow insertion of a multidomain therapeutic protein (e.g., GAA fusion protein) coding sequence into a target genomic locus such as an endogenous ALB locus and/or expression of the multidomain therapeutic protein (e.g., GAA fusion protein) coding sequence are also provided. The nucleic acid constructs and compositions can be used in methods of integration of a multidomain therapeutic protein (e.g., GAA fusion protein) nucleic acid into a target genomic locus, methods of expression of 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 method of preventing or reducing the onset of a sign or symptom of Pompe disease in a subject, including neonatal cells and subjects.

Abstract: Compositions and methods for expressing alpha 1 antitrypsin (AAT) in a host cell are provided. Also provided are compositions and methods for treating subjects having alpha 1 antitrypsin deficiency (AATD).