RAG1 lentiviral gene therapy restores T-cell development of RAG1-SCID patient cells in artificial thymic organoids.

ABSTRACT:

Abstract

Recombination activating gene 1 (RAG1) is essential for variable diversity joining recombination during early T- and B-cell development. Null mutations cause a complete block in receptor rearrangement, resulting in T-B- severe combined immunodeficiency (SCID). Patients with RAG1-SCID require hematopoietic stem cell transplantation for survival. Our phase I/II clinical trial (NCT04797260) is currently evaluating lentiviral RAG1 gene addition in autologous hematopoietic stem and progenitor cells (HSPCs). However, studying early human T-cell development is challenging due to limited access to thymic tissue. The artificial thymic organoid (ATO) system offers a promising in vitro model to study human T-cell differentiation. Here, we show that ATO cultures efficiently support T-

SUBMITTER: Meng X 

PROVIDER: S-EPMC12666348 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature