Overview
- A dual-particle CRISPR approach edited circulating T cells to insert a chimeric antigen receptor at a defined genomic on-switch site inside living animals.
- In humanized mouse models, a single infusion produced high frequencies of engineered cells and cleared aggressive leukemia within two weeks, with activity also seen against multiple myeloma and a sarcoma.
- One particle targeted T cells via anti-CD3 to deliver CRISPR-Cas9, while a second carried donor DNA encoding the CAR with instructions for site-specific integration.
- The study reports the first targeted integration of a large DNA sequence into human T cells in vivo and found this outperformed conventional random viral insertion.
- In-body–generated cells showed greater stemness and proliferative capacity than lab-made counterparts, and the team has formed Azalea Therapeutics to advance the platform toward clinical development.