DMA4-H228
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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.
| CAS No. | Not available |
| Chemical Name | CICL-1 (L829) |
| Synonyms | L-829, L 829, Capstan-lipid-CICL-1, Capstanlipid CICL1, CICL1, CICL 1, CICL-1, Lipid 829, L-829, L 829, Compound A-11, DC60860 |
| SMILES | CCCCCCCCC(=O)OCC(COC(=O)CCCCCCCC)CC(=O)OCCN(CCOC(=O)CC(COC(=O)CCCCCCCC)COC(=O)CCCCCCCC)C(=O)OCCN(C)C |
| Formula | C55H100O14N2 |
| M.Wt | 1,013.40 |
| Purity | >98% |
| Storage | Pure form: −20 °C, 1 year; In solvent: −80 °C, 6 months; −20 °C, 1 month. Sealed and protected from light. |
| Shipping condition | Ships from Shanghai. Pure lipid is stable during ice-pack transport. |
| Publication | Hunter TL, Bao Y, Zhang Y, et al. In vivo CAR T cell generation to treat cancer and autoimmune disease. Science. 2025;388(6753):1311-1317. |
| Component | mol% | Role |
|---|---|---|
| L829 (CICL-1) | Not reported | Ionizable lipid |
| Anti-CD8 targeting-moiety lipid conjugate (lipid identity not reported in supplied main article) | Not reported | Targeting-lipid conjugate |
| Three additional lipid components (identities not reported in supplied main article) | Not reported | Additional lipid components |
| Reported total | Not reported | Source values retained |
At 30 µg, four of five mice showed near-complete tumor clearance two days after the first dose, and all five did so three days after the second dose.
CD8-L829-tLNP-CD19; IV 30 µg; twice weekly for five doses; human PBMC plus Nalm6 xenograft · Figure 3G and main text, Science p. 1315The study reported lower liver and spleen luciferase expression with untargeted L829 LNP than with the ALC-0315 benchmark, and rapid L829 clearance from mouse liver while ALC-0315 remained elevated for at least seven days.
Luciferase mRNA and LC-MS studies; WT C57BL/6 mice · Figure 1B,C and main text, Science pp. 1311-1312Rat CD5-L829 tLNP was reported as tolerated up to 5 mg/kg without adverse observations, and a single 3 mg/kg IV dose was reported as safely administered in cynomolgus monkeys. In the repeat-dose anti-CD20 study, however, one monkey in the 1.5 mg/kg group developed a serious immune-effector-cell-associated event 72 h after the third dose and was euthanized.
Study-specific targeted L829 tLNPs; rat and cynomolgus-monkey experiments · Figure 1D,E; main text, Science pp. 1311 and 1316The product molecular weight is prefilled when available and remains editable. Confirm solvent compatibility and solubility before preparation.
Solvent volumes update from the molecular weight above.
| Mass | 1 mM | 5 mM | 10 mM |
|---|---|---|---|
| 10 mg | 9.8678 mL | 1.9736 mL | 986.78 μL |
| 25 mg | 24.6694 mL | 4.9339 mL | 2.4669 mL |
| 50 mg | 49.3389 mL | 9.8678 mL | 4.9339 mL |
| 100 mg | 98.6777 mL | 19.7355 mL | 9.8678 mL |
| 250 mg | 246.6943 mL | 49.3389 mL | 24.6694 mL |
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