ABE8.20-NRCH

ABE8.20-NRCH is an adenine base editor (ABE) variant developed to treat NEMO immunodeficiency (NEMO-ID), an X-linked disorder caused by mutations in the IKBKG gene. The editor consists of a high-activity adenine deaminase (ABE8.20) fused to a CRISPR-Cas9 variant with an expanded NRCH protospacer adjacent motif (PAM) recognition sequence. This specific configuration allows for the precise targeting and correction of the c.768+5 G>A mutation in the IKBKG gene, which otherwise leads to aberrant splicing and a truncated NEMO protein. By converting the mutated adenine back to guanine, ABE8.20-NRCH restores proper gene splicing and protein expression. The therapy is intended for use in an autologous hematopoietic stem cell transplantation (HSCT) framework, where a patient's own CD34+ cells are edited ex vivo and then re-infused.