Determining the Primary Source of ABE in NILV-Transduced Cells for SCID-A Gene Correction

Abstract

SCID-A, severe combined immunodeficiency caused by a deficient artemis protein, is a genetic disorder that causes patients to possess essentially no functional T and B cells. This genetic disorder is commonly found in the Navajo and Apache nations who speak the Athabaskan language. The deficient artemis protein is involved in V(D)J recombination, which is a process in lymphocytes that combines V(D)J gene segments that allow the lymphocytes to create T and B cell receptors. With SCID-A, patients struggle to produce sufficient T and B cell receptors to have a healthy immune system and cannot fight infections. Without treatment, this disease is fatal. Adenine Base Editing (ABE) is a promising tool for correcting the SCID-A mutation, but safe and effective delivery methods remain a major challenge in translating this approach into clinical trials. Non-integrating lentivirus (NILV) is being explored as a delivery vehicle for ABE as it is able to be loaded with a large package (ABE + sgRNA) and not remain integrated into the genome of the cells.