Fuente: WIPO "tomato" The disclosure compositions and methods for non-genotoxic conditioning with an anti-CD45 antibody, anti-CD45 antibody drug conjugate, or anti-CD45 chimeric antigen receptor expressing T cell. The methods involve altering a CD45 polynucleotide sequence in an HSPC using a base editor to encode a CD45 polypeptide with reduced binding to the antibody. Embodiments of the disclosure also feature compositions and methods for treating diseases and conditions by non-genotoxic conditioning with an anti-CD45 antibody, anti-CD45 antibody drug conjugate, or anti-CD45 chimeric antigen receptor expressing T cell (CAR-T) prior to, simultaneously with, or after transplant of the based edited HSPC. The compositions and methods disclosed herein advantageously can reduce or eliminate the use of genotoxic agents such as busulfan, and provide edited HSPCs that are resistant to the disclosed anti-CD45 antibody, anti-CD45 antibody drug conjugate, and anti-CD45 chimeric antigen receptor expressing T cell.