Биологическая активность
CICL1 (L829) is a novel ионизируемый cationic липид specifically engineered for targeted липид 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-клетка 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.
Оригинал на английском
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.
Химические свойства
- Брутто-формула
- C₅₅H₁₀₀O₁₄N₂
- Мол. масса
- 1013.40 г/моль
- SMILES
- CCCCCCCCC(=O)OCC(COC(=O)CCCCCCCC)CC(=O)OCCN(CCOC(=O)CC(COC(=O)CCCCCCCC)COC(=O)CCCCCCCC)C(=O)OCCN(C)C
- Синонимы
- L-829，L 829,Capstan-lipid-CICL-1，Capstanlipid CICL1, CICL1 , CICL 1
3D-структура молекулы
Вращайте мышью · Колесо — масштаб
Хранение и физические свойства
- Условия хранения
- 1 года -20°C Publication: 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.
Безопасность и документация
Только для научно-исследовательского применения. Не предназначено для использования у пациентов или в качестве лекарственного средства.