Abstract: The present invention relates to compositions, systems, and methods for editing a disease/condition causing mutation region in a target gene in a cell. In certain embodiments, the following components are employed: i) mRNA encoding a Tumor Protein p53 (TP53) inhibitor, ii) an inhibiting agent that inhibits Tumor Suppressor p53-Binding Protein 1 (53BPI) (e.g., small molecule EoHR or mRNA encoding a protein that inhibits 53BPI), iii) mRNA encoding a Cas nuclease for CRISPR; iv) a guide RNA specific for a target cleavage site proximal to said disease/condition-causing mutation region; and v) a repair template comprising a region of interest configured to replace said disease/condition-causing mutation region in the target gene during homology-directed repair (HDR). In certain embodiments, the cell is a T-cell, stem cell (e.g., hematopoietic stem cell), or progenitor cell from a subject with the disease or condition (e.g., a Primary Immunodeficiency Disease (PID)).