| Parameter | Value |
|---|---|
| Catalog number | DCL0013 |
| Product name | iL-19 |
| Aliases | iL19; iL 19; IL-19; IL 19; iL-19 lipid |
| Molecular formula | C62H125N3O8 |
| Molecular weight | 1040.70 g/mol |
| SMILES | CC(C)CCCC(C)CCN(CCOCCOC(=O)CCCCN(CCCCC(=O)OCCOCCN(CCC(C)CCCC(C)C)CCC(C)CCCC(C)C)CCOCCO)CCC(C)CCCC(C)C |
| CAS number | Not reported |
| Purity / availability | >95% by ELSD-HPLC |
| Salt / stereochemistry | Neutral structure; no counterion depicted; four tail stereocenters unassigned |
| Storage | Follow batch-specific handling and storage documentation |
| Categories | Cationic/Ionizable Lipids; Ionizable Lipids for circRNA Delivery; Ionizable Lipids for Muscle Delivery |
Structure derived from Main Fig. 3 and SI p. 24, verified against S9 on SI p. 15. HRMS [M+H]+: calculated 1040.9539, found 1040.9538. This is not the average molecular weight. Batch-specific test results are provided in the issued COA.
Formulation
Literature formulation
Component order below is standardized as iL-19 / DSPC / cholesterol / DMG-PEG2000. The paper lists cholesterol before DSPC; the formulation itself is unchanged.
| Component | Company product | mol% | Molecular weight (g/mol) |
|---|---|---|---|
| iL-19 | DCL0013 | 50 | 1040.70 |
| DSPC | DC57005 | 10 | 790.15 |
| Cholesterol | DCD-041 | 38.5 | 386.65 |
| DMG-PEG2000 | DC40169 | 1.5 | Confirm complete-conjugate batch average |
Total: 100 mol%. Ionizable (cationic) lipid:circRNA mass ratio: 30:1. N/P ratio: not reported. The 30:1 ratio is not a total-lipid:RNA ratio and is not N/P.
Source: Main p. 4; SI §2, p. 3; §5.1, p. 27; §6.3, p. 34 [1].
Component mass calculator
Calculate lipid amounts from total lipid quantity. PEG2000 is a chain designation; the complete conjugate molecular weight must be confirmed for the batch.
| Component | MW | mol% | µmol | mg | Mass % |
|---|
Calculated mg = total µmol × mol% ÷ 100 × MW ÷ 1000. Mass fractions use the summed component mass. No RNA amount or N/P is inferred.
Preparation details & reproducibility notes
| Parameter | Literature information |
|---|---|
| Organic stocks | iL-19 25 mg/mL; cholesterol 20 mg/mL; DSPC 20 mg/mL; DMG-PEG2000 10 mg/mL, all in anhydrous ethanol |
| Aqueous phase | circLuc in 10 mM sodium citrate, pH 5.0; citrate buffer contains 20% (w/v) sucrose |
| Mixing | Rapid pipette mixing; reported organic:aqueous volume ratio 1:3 |
| Mixing equipment / flow | No microfluidic flow rate reported; do not substitute a microfluidic protocol as the published method |
| IM preparation | Diluted with PBS, pH 7.4, to 66.5 µL; 33 µL per quadriceps reported |
| IV preparation | Diluted with PBS, pH 7.4, to 100 µL; preliminary retro-orbital administration |
| Post-processing | No dialysis, ethanol-removal or sterile-filtration step specified in the supplied protocol |
| Formulated-LNP storage study | 4 °C for 14 days; monitored size, PDI and zeta potential. This is not a validated shelf life for the supplied neat lipid. |
Source: SI §2, pp. 3–5; §6.5, p. 39 [1].
Formulation optimization
The authors varied helper lipids, sterols and lipid:circRNA mass ratios. The standard iL-19 formulation remained the preferred condition in the tested IM screen; substituting DOPE or alternative sterols reduced the displayed expression.
| Condition | Relative expression vs standard iL-19 |
|---|---|
| Standard iL-19, 30:1 mass ratio | 100% |
| DOPE replacing DSPC | 92% |
| β-Sitosterol replacing cholesterol | 63% |
| Fucosterol replacing cholesterol | 71% |
| Mass ratio 10:1 / 20:1 / 40:1 | 67% / 90% / 96% |
| Mass ratio 50:1 / 60:1 / 70:1 / 80:1 / 90:1 / 100:1 | 83% / 71% / 56% / 57% / 52% / 63% |
Female BALB/c mice, IM, circLuc, figure-labeled dose 1.5 µg, 12 h; n = 2. Percentages are printed figure labels, not a statistical proof that every pair differs. No error bars are reconstructed.
Source: SI Fig. S7, p. 34 [1].
Physicochemical properties: circRNA vs linear mRNA
| Cargo | Size (nm) | PDI | Zeta (mV) | Apparent pKa | EE (%) |
|---|---|---|---|---|---|
| circLuc | 128 ± 3 | 0.11 ± 0.02 | 28.1 ± 2.1 | 6.7 ± 0.09 | 92 ± 0.5 |
| Linear mFluc | 150 ± 5 | 0.15 ± 0.03 | 11.6 ± 0.9 | 6.8 ± 0.03 | 87 ± 0.2 |
Reported mean ± SD, triplicate measurements. Size/PDI/zeta: DLS; encapsulation: RiboGreen; apparent LNP pKa: TNS fluorescence titration (half-maximal fluorescence). These are formulated-particle values, not intrinsic properties of neat iL-19.
Source: SI Table S6, p. 27; Table S7, p. 30; methods pp. 3–4 [1].
Reference
Cook A, Yadav PK, Helmy EW, Vlasova K, Chang HY, Wender PA. Circular RNA Delivery In Vitro and In Vivo Using Doubly Branched Aminoethoxy-Functionalized Ionizable Lipid Nanoparticles. Journal of the American Chemical Society (2026). DOI: 10.1021/jacs.6c14175. Main article (9 PDF pages) and Supporting Information (85 pages). Volume and final pagination are not assigned in the supplied version.
Performance
Why iL-19 is the overall lead
iL-19 and iL-20 were both strong C2C12 candidates: the plotted expression values are 2800% and 2890% of SM-102, respectively. iL-20 is numerically higher in that cell assay, but the authors selected iL-19 as the overall lead based on the combined structure–delivery and in vivo IM evidence. The study does not establish iL-19 as best for every route or payload.
Source: Main Figs. 3–4, pp. 4–5; SI Figs. S10–S11, pp. 37–38 [1].
In vitro circRNA expression: C2C12 myocytes
| Lipid | Relative expression (SM-102 = 100%) |
|---|---|
| SM-102 | 100 |
| iL-15 | 1032 |
| iL-16 | 1323 |
| iL-17 | 1441 |
| iL-18 | 1665 |
| iL-19 | 2800 |
| iL-20 | 2890 |
circLuc, 60 ng per well; 15,000 cells seeded per well; 12-hour expression readout. Main Fig. 3 reports n = 6 independent experiments, with SD and one-way ANOVA/Dunnett versus SM-102 (all six second-generation lipids P < 0.0001). The general SI procedure additionally describes triplicate wells; these are not substituted for the figure-specific n.
HEK293T experiments provide supporting evidence of the structure–delivery trends (SI Figs. S4–S6, n = 3). Cell luminescence is a protein-expression endpoint, not an editing rate.
Source: Main Fig. 3, p. 4; SI methods pp. 4–5 and Figs. S4–S6, pp. 32–33 [1].
Intramuscular validation: benchmark comparison
Female BALB/c mice, 6–8 weeks, approximately 20 ± 2 g; circLuc; 12 h; n = 6 per group. The experiment is labeled 1.5 µg circLuc and uses bilateral quadriceps injections (33 µL per quadriceps). The text does not unambiguously resolve whether the labeled dose is per site or across both sites, so no total-dose conversion is made here.
Original display of the rounded percentages printed in SI Fig. S11; numeric SD is not tabulated and is not reconstructed. SM-102 is normalized to 100%.
The authors report iL-19 expression approximately 2.5× SM-102, 7.8× ALC-0315, 33.4× DLin-MC3-DMA and 2.3× δO3. These reported fold values are retained rather than recalculated from rounded bar labels.
Benchmark LNPs used their respective published optimized formulations. The comparisons share the study model, cargo and readout, but do not use one identical lipid composition for every benchmark. One-way ANOVA/Dunnett tested comparisons against SM-102; iL-19 P < 0.0001. Significance is not inferred for each iL-19-versus-benchmark pair.
Source: Main p. 5 and Fig. 4; SI Fig. S11, p. 38 [1].
A separate extended IM screen used n = 4 per group (SI Fig. S10, p. 37). Its data are not pooled with the n = 6 benchmark study.
Preliminary intravenous experiment
In BALB/c mice given 3.3 µg circLuc by retro-orbital IV injection, 12-hour expression for iL-19 was plotted at 118% of SM-102 (100%), with n = 2. The authors describe efficacy as comparable, with qualitative liver localization. This small study does not establish statistically significant superiority, quantitative liver selectivity or performance in other organs.
Source: SI §6.5 and Fig. S12, p. 39 [1].
Structure–delivery analysis
Observed SAR
Across the tested library, doubly branched tails and aminoethoxy units were associated with improved circLuc delivery. iL-19 combines a triamine scaffold, ester linkages, aminoethoxy segments and four 3,7-dimethyloctyl tails. Adding silane motifs did not improve the tested circRNA expression.
Interpretation & limits
Hydrogen bonding, ionization and biodegradability guided the design. These rationales do not establish a measured receptor-targeting mechanism or a product-specific in vivo degradation half-life. Several analogs change more than one feature; individual causal contributions cannot always be isolated.
Source: Main Figs. 2–3 and Results pp. 3–5; SI iL-19 p. 24 and precursor S9 p. 15 [1].
Stability & tolerability
Size, PDI and zeta potential showed negligible changes during the reported 14-day LNP storage study at 4 °C. This does not establish RNA integrity, preserved expression over that entire period, frozen-product shelf life or shipping stability.
Mice showed normal behavior, no observed acute clinical signs and no reported weight loss during the study. The authors specifically identify the positively charged lead formulations as needing further safety, immunogenicity and PK/PD evaluation. No clinical safety claim or vaccine-protection outcome is established.
Source: Main p. 5; SI Figs. S1–S3, pp. 28–29 [1].
Full reference
Cook A, Yadav PK, Helmy EW, Vlasova K, Chang HY, Wender PA. Circular RNA Delivery In Vitro and In Vivo Using Doubly Branched Aminoethoxy-Functionalized Ionizable Lipid Nanoparticles. Journal of the American Chemical Society (2026). DOI: 10.1021/jacs.6c14175. Main article (9 PDF pages) and Supporting Information (85 pages). Volume and final pagination are not assigned in the supplied version.
Product documents
All guides are readable online and support browser printing. A batch-specific COA and approved SDS must be requested for the supplied product.
Reference
Cook A, Yadav PK, Helmy EW, Vlasova K, Chang HY, Wender PA. Circular RNA Delivery In Vitro and In Vivo Using Doubly Branched Aminoethoxy-Functionalized Ionizable Lipid Nanoparticles. Journal of the American Chemical Society (2026). DOI: 10.1021/jacs.6c14175. Main article (9 PDF pages) and Supporting Information (85 pages). Volume and final pagination are not assigned in the supplied version.