MND-c.o.RAG1 lentivirus (LV) efficiently transduces HSPCs from RAG1-SCID patients. (A) Schematic representation of the location of the RAG1 mutations in the 3 RAG1-SCID patients, including the specific mutation and the cell count of CD3, CD4, and naïve CD4 cells per microliter of blood. The N-terminal noncore domain consists of a series of basic motifs (not depicted) and a domain formed by a RING finger and zinc finger motif. The core domain consists of NBD, DDBD, PHD, preR, RNH, zinc-binding domain, and the CTD. Based on Notarangelo et al. with permission.1 (B) Experimental setup created with biorender.com. Canté-Barrett, K. (2025) https://biorender.com/gz8bj0t (C) Primeflow analysis of patient samples 1 to 3 before and after LV transduction with MND-c.o.RAG1. RPL13a: housekeeping mRNA, c.o.RAG1: codon-optimized RAG1 mRNA, as measured by flow cytometry. CTD, carboxy-terminal domain; DDBD, dimerization and DNA-binding domain; NBD, nonamer-binding domain; PHD, plant homeodomain; preR, pre-RNase H; pt, patient; RNH, catalytic RNase H.
