DMA4-H228
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CICL-1 (catalog alias L829) is an ionizable lipid for targeted RNA-delivery research. The cited L829 study reports in vivo CAR expression, B-cell depletion and leukemia-model activity using antibody-targeted LNPs, with a serious adverse event in a repeat-dose primate study. The catalog lipid is supplied for research; the reported outcomes depend on the complete LNP, targeting ligand and RNA cargo.
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Mouse and nonhuman-primate evidence for L829, with targeting, efficacy and tolerability kept separate.
The catalog mapping to L829 is retained from the existing approved record. The Science main article does not independently establish the commercial structure or the Compound A-11 alias.
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| L829 / CICL-1 | DC99010 | 1013.4 | Not assigned | Not calculable from disclosed data |
| Targeting ligand-lipid conjugate | Not uniquely mapped | Not established | Not assigned | Not calculable from disclosed data |
| Other three lipid components | Not uniquely mapped | Not established | Not assigned | Not calculable from disclosed data |
The molecular weight shown for CICL-1 is a catalog value. Complete five-lipid identity, proportions and N/P await Supplementary Table S1; no patent formulation is substituted.
Not all inputs are assigned to a single verified study formulation; unassigned fields are blank. Enter your own values to calculate a research scenario. Molecular weights and ratios are editable. Results are calculated, not measured study data. No N/P or RNA dose is inferred.
| Component | MW | Molar ratio | Mass (mg) | Mass % |
|---|---|---|---|---|
| L829 / CICL-1 | ||||
| Targeting ligand-lipid conjugate | ||||
| Other three lipid components |
| Item | Evidence |
|---|---|
| Source compound | L829 in Hunter et al., Science (2025). CICL-1 / Compound A-11 is the catalog mapping; those names and a chemical structure are not disclosed in the reviewed main paper. |
| Targeting | Untargeted LNP, CD5-targeted LNP and CD8-targeted LNP are separate systems. Targeting ligand and cargo influence performance. |
| Composition | Five-lipid formulation is referenced to Supplementary Table S1. Exact component identities, molar ratios and N/P remain unverified without that table. |
| Particle properties | Size, PDI, encapsulation and apparent pKa are not assigned from unrelated patents. |
Hunter et al., main article and references to supplementary methods; existing reviewed main-article record retained. New SI retrieval was blocked on 28 October 2026.
| Experiment | Reported outcome | Context / source |
|---|---|---|
| Untargeted reporter LNP | Less liver and spleen luciferase expression than the ALC-0315 benchmark. | Wild-type C57BL/6 mice; main Fig. 1B. Reporter expression is distinct from particle accumulation. |
| Lipid persistence | L829 cleared more rapidly from mouse liver; ALC-0315 remained elevated for at least 7 days. | Main Fig. 1C; compound clearance endpoint, not RNA expression duration. |
| Humanized leukemia model | Near-complete tumor clearance in 4/5 mice two days after the first dose; 5/5 three days after the second dose. | CD8-targeted anti-CD19 CAR mRNA; PBMC/Nalm6 xenograft, 30 micrograms IV, twice weekly for five doses; Fig. 3G. |
| Endpoint | Reported result | Study context |
|---|---|---|
| Peripheral B cells | Decline by 6 hours and near-undetectable levels by 24 hours after the first dose. | CD8-targeted anti-CD20 CAR mRNA; 22 cynomolgus monkeys across three studies, 0.1-2.0 mg/kg, three IV doses 72 hours apart; Fig. 4. |
| CD8 T-cell CAR expression | Up to 85% after the third dose. | Upper observed value, not mean or guarantee; minimal CD4 T-cell CAR expression reported. |
| CD8 NK-cell CAR expression | Up to 95% after the third dose. | Dose-dependent response; Fig. 4C. |
| B-cell recovery | Repopulation started around day 21 and approached baseline by day 35. | 1-1.5 mg/kg follow-up; Fig. 5. Predominantly naive repopulation was interpreted by the authors as suggestive of immune reset. |
| Study | Finding | Interpretation |
|---|---|---|
| Rat CD5-targeted L829 | Reported tolerated up to 5 mg/kg without adverse observations. | Main Fig. 1D; does not establish the safety of every cargo/targeting combination. |
| Single-dose cynomolgus study | A 3 mg/kg IV dose was reported as tolerated. | Main Fig. 1E; separate from repeat CAR dosing. |
| Repeat anti-CD20 CAR dosing | One monkey in the 1.5 mg/kg group developed a serious immune-effector-cell-associated event 72 hours after dose 3 and was euthanized. | Main text p. 1316. This event must be considered alongside depletion efficacy; no blanket nontoxic claim. |
Mouse and primate results: Figures 1 and 3-5 — Original source figures.
| 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 | 1013.40 |
| Purity | >95% by ELSD-HPLC |
| 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 |
The 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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