Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy

Study Description: This is a phase 1/2, non-randomized study of a single infusion of autologous hematopoietic stem/progenitor cells base-edited to repair interleukin 2 receptor gamma (IL2RG) mutations (BE-HSPC IL2RG) in 18 participants with X-linked severe combined immunodeficiency (X-SCID). Primary Objective: Evaluate the safety of treatment with BE-HSPC IL2RG in participants with X-SCID. Secondary Objectives: Evaluate efficacy of treatment with BE-HSPC IL2RG in participants with X-SCID. Exploratory Objectives: 1. Evaluate off-target (OT) editing activity. 2. Compare outcomes of immune reconstitution with lentivector (LV) gene therapy. Primary Endpoint: Safety of treatment with BE-HSPC IL2RG, by quantifying frequency and severity of adverse events (AEs) related to study agent from infusion to 12 months after infusion. Secondary Endpoints (24 months post-study agent infusion): 1. Percentage of participants with \>=5% mutation-repaired myeloid cells. 2. Editing efficiency in peripheral blood cells (such as T, B, and natural killer \[NK\] cells). 3. Immune reconstitution: 1. T, B, and NK cell number improvement from baseline. 2. Emergence of naive T cells and CD31+ recent thymic emigrants. 3. B-cell function: immunoglobulin (Ig) production. 4. Specific responses to vaccines. 4. Clinical efficacy: improvement from baseline problems such as recurrent infection, chronic norovirus, protein-losing enteropathy, gastrointestinal complaints, growth failure, malnutrition, or immune dysregulation. 5. Frequency and severity of all study agent-related AEs and serious adverse events (SAEs) from time of study product infusion. Exploratory Endpoints: 1. Evaluate for frequency of off-targets (OTs) by high-throughput sequencing (HTS) of the target mutation at 2 years post-infusion. 2. Compare rates of immune reconstitution with LV-X-SCID gene therapy.