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.
Cat.No
DC99010
Name
Capstan lipid CICL-1(L829)
Chemical Properties
CAS
Formula
MW
Storage
-20
References
Hunter TL, June CH, Aghajanian H etl. In vivo CAR T cell generation to treat cancer and autoimmune disease. Science. 2025 Jun 19;388(6753):1311-1317.
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