Azalea Therapeutics has developed technology for the construction of CAR-T cells directly in the body (in vivo) using precise gene editing and enveloped delivery vehicles (EDV). In preclinical studies in mice with hematologic and solid tumors, their in vivo engineered TRAC-inserted CAR-T cells showed potent antitumor activity and completely eradicated tumors. A single dose without ex vivo production or lymphodepletion produced potent and persistent CAR-T cells with physiologically regulated CAR expression. Studies in primates have shown complete aplasia of CD20+ B cells in peripheral blood by day 10 after a single intravenous dose of EDV + AAV. TRAC-CAR T cells expanded to approximately 35% of peripheral T cells and achieved complete aplasia of CD20+ B cells in lymph nodes and bone marrow by day 13. The technology ensures targeted delivery to T cells and integration of the CAR into a precise genomic location for greater safety and efficacy.[1][2]