Capstan lipid CICL-1 (L829)

CICL1 (L829) ​​ is a ​​novel ionizable cationic lipid​​ specifically engineered for ​​targeted lipid nanoparticles (tLNPs) ​​ that enables efficient in vivo delivery of mRNA payloads to ​​CD8+ T cells​​. Designed to overcome limitations of conventional LNPs, CICL-1 (L-829) ​​significantly ​​reduces off-target delivery to the liver​​ and exhibits ​​rapid clearance​​ compared to benchmark lipids like ALC-0315, while demonstrating ​​enhanced biodegradability and tolerability​​ in rodent and primate models. When incorporated into CD8-targeted tLNPs, CICL 1 (L829 enables ​​preferential transfection of CD8+ T cells​​ over other immune subsets, facilitating the generation of functional ​​anti-CD19 or anti-CD20 CAR T cells directly *in vivo​​*. These tLNP-engineered CAR T cells mediate ​​rapid, deep B-cell depletion​​ in humanized mice and cynomolgus monkeys, with repopulating B cells exhibiting a naïve phenotype suggestive of immune reset. By eliminating the need for ex vivo manufacturing or lymphodepleting chemotherapy, the L829-tLNP platform represents a ​​safer, scalable approach​​ for accessible CAR T therapy in oncology and autoimmune diseases.