Chemical structureResearch use only

CAT. NO. DC60465

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Lipid R6

Pack size & price

USD

Add formulation componentsThree supporting lipids, 100 mg each+US$450 / set

DOTAP chloride · DC33636 · 100 mg
Cholesterol · DCD-041 · 100 mg
DMG-PEG2000 · DC40169 · 100 mg

The add-on covers all three components supplied separately. R6 is charged at its selected pack price; RNA, buffer and formulation service are not included. This is a component supply option. The conflicting published optimized ratios require resolution before reproducing that formulation.

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Ships from ShanghaiIce-pack transportPure lipid recommended

Product overview

Description & Application

Lipid R6 is an AGILE-identified ionizable lipid for macrophage mRNA delivery research. Its acyclic diethylaminopropyl headgroup is linked to an asymmetric, saturated amino-amide scaffold. R6 LNPs supported higher mRNA-derived expression than H9 and MC3 LNPs in RAW 264.7 macrophages in the cited study. The reported GFP-positive population was 51.0% under the specified in vitro conditions. Its activity was cell-type dependent: H9 performed better in HeLa cells and muscle delivery. R6 is supplied as the lipid building block; formulation-specific results and composition discrepancies are detailed below.

Related products & formulation components

Product	Role
DOTAP chloride	Cationic helper in the R6 formulation study
Cholesterol	Sterol component
DMG-PEG2000	PEG-lipid component
Lipid H9	Cell-type comparator from the same AGILE study
MC3	Benchmark lipid
ALC-0315	Benchmark lipid

Parameter	Value
Chemical Name	Lipid R6
CAS No.	Not available
Synonyms	R6; Lipid-R6; R-6 lipid; AGILE R6; 2-((3-(diethylamino)propyl)amino)-N-undecylheptadecanamide
Formula	C35H73N3O
M.Wt	551.99
SMILES	CCCCCCCCCCCCCCCC(NCCCN(CC)CC)C(=O)NCCCCCCCCCCC
Purity	>95% by ELSD-HPLC
Storage	−20 °C; unopened, protected from light and moisture. Follow the supplied batch expiry/retest date.
Publication	Xu, Y.; Ma, S.; Cui, H.; et al. AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery. Nature Communications 2024, 15, 6305. DOI: 10.1038/s41467-024-50619-z

View original study figures ↓

Research application and evidence scope

R6 was selected from the AGILE candidates for RAW 264.7 macrophage transfection. Its activity is cell-type dependent and is not evidence of universal superiority or in vivo macrophage targeting. H9 is the separate lead for the muscle-delivery experiments.

Values shown are literature-reported results for the cited formulation and study conditions. They do not guarantee performance of the supplied product in other formulations or experiments.

Formulation records and source discrepancy

Record	Component order and reported values	Weight ratio / N/P	Interpretation
Initial library screening	Ionizable lipid / DOPE / cholesterol / C14-PEG2000 = 35:16:46.5:2.5	Screening stage uses crude lipid yield estimates. N/P not reported.	Sum 100; do not conflate with optimized R6.
Pre-optimization H9/R6 comparison	Ionizable lipid / DOTAP / cholesterol / DMG-PEG2000 = 35:16:46.5:2.5	General manual formulation: ionizable lipid:mRNA = 10:1 by mass. N/P not reported.	Sum 100; Methods description.
R6 optimized — Methods text	R6 / DOTAP / cholesterol / DMG-PEG2000 = 60:15:42.7:1.6	An optimized weight ratio is not assigned unambiguously here. N/P not reported.	Sum 119.3 molar parts, not 100 mol%.
R6 top DoE run #2 — SI Table 4	R6 / DOTAP / cholesterol / PEG = 60:15:17:0.5	Lipid:mRNA weight ratio 7.5:1; the table does not further define the lipid basis. N/P not reported.	Sum 92.5; RAW 264.7 response 6.680 on a Log2 scale.

The main-text optimized ratio and SI top run #2 disagree. Both are retained as separate source records. The manuscript does not resolve which composition maps to every later performance panel. The normalized tables below are arithmetic illustrations, not a corrected or validated preparation recipe.

Source: Main Methods, “LNP formulation and characterization”; SI p.19, Table 4, run #2.

Component molecular weights and mass tables

Calculated basis: 10 µmol total lipid components. Mass = component amount × MW / 1000 in mg. DOTAP uses the catalog chloride-salt MW; DMG-PEG2000 uses 2507. The SI table labels its PEG component only as “PEG”; using DMG-PEG2000 for that table is a mapping to the main Methods, not an independent identity measurement.

Pre-optimization composition

Component	MW	Reported molar values	Calculated normalized mol%	Calculated mg at 10 µmol	Calculated mass fraction
Lipid R6	551.99	35	35.0000	1.9320	35.29%
DOTAP chloride	698.555	16	16.0000	1.1177	20.42%
Cholesterol	386.65	46.5	46.5000	1.7979	32.84%
DMG-PEG2000	2507	2.5	2.5000	0.6268	11.45%

Methods optimized ratio — unresolved

Component	MW	Reported molar values	Calculated normalized mol%	Calculated mg at 10 µmol	Calculated mass fraction
Lipid R6	551.99	60	50.2934	2.7761	51.65%
DOTAP chloride	698.555	15	12.5733	0.8783	16.34%
Cholesterol	386.65	42.7	35.7921	1.3839	25.75%
DMG-PEG2000	2507	1.6	1.3412	0.3362	6.26%

SI Table 4 run #2 — unresolved

Component	MW	Reported molar values	Calculated normalized mol%	Calculated mg at 10 µmol	Calculated mass fraction
Lipid R6	551.99	60	64.8649	3.5805	64.40%
DOTAP chloride	698.555	15	16.2162	1.1328	20.38%
Cholesterol	386.65	17	18.3784	0.7106	12.78%
DMG-PEG2000	2507	0.5	0.5405	0.1355	2.44%

For unformulated R6, 1 mg corresponds to 1.8116 µmol, and a 1 mM stock requires 0.55199 mg/mL. These chemical stock conversions do not establish solvent compatibility or an RNA formulation protocol.

Source: Reported composition: main Methods and SI Table 4. Normalized fractions and masses: calculated from catalog MW inputs.

Reported preparation and analytical methods

Mix the aqueous mRNA phase in 10 mM citrate buffer with the ethanol lipid phase at 3:1 v/v. The initial screening used an automated liquid handler, crude lipids and direct cell testing. Subsequent experiments used manual pipetting and dialysis against 1× PBS in a 20 kDa cutoff cassette for 6 h at 4 °C. The cited Methods do not state citrate pH, a microfluidic flow rate or an N/P value. The general 10:1 ratio refers to ionizable lipid:mRNA mass, not N/P.

Particle size, PDI and zeta potential were measured by light scattering/electrophoretic methods; RNA encapsulation used a RiboGreen assay. Apparent LNP pKa was determined from the half-maximum TNS fluorescence point over pH 2–11. An exact R6 pKa, particle size, PDI or encapsulation percentage is not assigned from the available R6-specific records.

Source: Main Methods, “LNP formulation and characterization”.

GFP mRNA delivery to RAW 264.7 macrophages

LNP	GFP-positive cells shown in Fig. 4g	Experiment
R6	51.0%	RAW 264.7; 500 ng GFP mRNA/well; 24-well plates; 48 h; 37 °C
ALC-0315	48.1%	Same displayed flow-cytometry comparison
MC3	9.80%	Same comparison
H9	6.76%	Same comparison
Untreated control	0.14%	Same comparison

These are the percentages displayed on the representative flow-cytometry distributions, not means with replicate uncertainty. From those displayed percentages, R6/MC3 is 5.20-fold and R6/H9 is 7.54-fold (calculated); no significant superiority over ALC-0315 is inferred from 51.0% versus 48.1%. Imaging was reported with n = 3; replicate GFP percentages are not provided in the downloaded Source Data sheet.

Source: Main Fig. 4f–g and Methods, “Transfection test in RAW 264.7 cells”.

Cell-type-specific luciferase expression

mTP is log₂(mean luminescence in treated cells / mean luminescence in untreated cells) at 24 h. It is not a transfected-cell percentage. General cell screening used 0.1 µg Fluc mRNA per well in 96-well plates.

Ionizable lipid	RAW 264.7 mTP, mean ± SD	HeLa mTP, mean ± SD	n
H9	4.790 ± 0.254	10.274 ± 0.436	6
MC3	6.909 ± 0.824	9.509 ± 0.249	6
R6	8.309 ± 0.389	7.917 ± 0.334	6

The values above are recalculated from the six source-data entries per group in Fig. 4e. R6 leads in RAW 264.7, whereas H9 leads in HeLa. The paper describes the R6/H9 comparison as composition-matched, but later Methods and SI optimized compositions differ; do not assign a single unverified optimized composition to this panel.

Source: Main Fig. 4e; Methods, “In vitro high-throughput screening”; Source Data, “Figure 4”, rows 9–11.

DoE improvement in RAW 264.7 cells

Record	Luciferase activity, mean ± SD (RLU)	n
R6 pre-DoE	70,550.5 ± 19,519.2	6
R6 post-DoE	107,760.7 ± 31,998.0	6

Calculated post/pre mean ratio: 1.53-fold. The source reports p = 0.0353. This RLU comparison is separate from the GFP-positive-cell endpoint and the Log2 DoE response.

Source: SI p.45 Fig. S26a; Source Data, “Supplementary Figure 26”, B2:C7.

All 17 R6 DoE runs from Supplementary Table 4

Run	Lipid:mRNA mass ratio	R6	DOTAP	PEG	Cholesterol	RAW 264.7 response (Log2)
1	7.5	60	20	1.5	11	6.518
2	7.5	60	15	0.5	17	6.680
3	15	30	10	1.5	43.5	4.327
4	7.5	30	20	2.5	40	4.414
5	7.5	30	10	2.5	50	2.705
6	7.5	60	10	2.5	20	2.825
7	15	60	10	2.5	12.5	3.102
8	15	60	20	0.5	4.5	5.172
9	15	60	10	0.5	14.5	5.574
10	11.25	60	20	2.5	6.25	5.115
11	15	45	20	2.5	17.5	4.621
12	7.5	45	10	0.5	37	6.123
13	15	30	20	0.5	34.5	5.604
14	11.25	45	15	1.5	27.25	3.333
15	15	30	15	2.5	37.5	3.628
16	7.5	30	20	0.5	42	6.443
17	11.25	30	10	0.5	48.25	5.150

Values are transcribed in the original column order. Rows are not silently adjusted to total 100. Run #2 is marked as the top performer by the authors.

Source: SI p.19, Table 4.

In vivo boundaries and vaccine results

Experiment	Reported observation	Conditions
Muscle luciferase expression	R6 was lower than H9; does not support a general muscle-delivery advantage.	Intramuscular Fluc mRNA, 0.2 mg/kg; 6 h; two mice/group; SI S27b.
Cy5-labelled RNA distribution	Strong injection-site signal with lower liver and spleen signal; fluorescence is not functional transfection.	C57BL/6J; intramuscular Cy5-mLuc RNA, 0.3 mg/kg; 6 h; n = 3; SI S28a.
OVA vaccination	R6 induced lower anti-OVA IgG than ALC-0315 in the reported prime–boost study.	10 µg mOVA per administration; day-28 antibody readout; SI S28b.
Tolerability	Limited cell-viability and day-28 liver-enzyme studies were reported; no clinical safety inference.	SI S27a and S28c–d.

Source Data S28b contains four titers per group: R6 400, 200, 800, 800; ALC-0315 51,200, 102,400, 51,200, 25,600. Their arithmetic means are 550 and 57,600 (calculated), with source p = 0.0021 for R6 versus ALC-0315. The SI caption includes n = 3, so the four-entry antibody dataset is reported separately rather than silently changing the replicate count. R6 is therefore presented for macrophage transfection research, not as the best vaccine lipid in this study.

Source: SI pp.46–47, Figs. S27–S28; Source Data, “Supplementary Figure 28”.

Product identity

Lipid R6 is a neutral amino-amide with molecular formula C35H73N3O and molecular weight 551.99. Stereochemistry is not specified.

References

Xu, Y.; Ma, S.; Cui, H.; et al. AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery. Nature Communications 2024, 15, 6305. DOI: 10.1038/s41467-024-50619-z.

Supplementary Information, pp. 1–57 · Source Data workbook.

Study content is paraphrased and calculations are identified; source article licensed under CC BY 4.0.

Published study figures

Original publication figures illustrating the cited formulation and biological results. Select an image to view it at full size.

Figure 4: R6, H9 and benchmark LNPs are compared in RAW 264.7 and HeLa cells. Panels e–g show measured reporter expression, microscopy and flow cytometry; panels a–c show model predictions, not experimental efficacy. — Figure 4 — R6 and H9 show cell-dependent delivery
R6, H9 and benchmark LNPs are compared in RAW 264.7 and HeLa cells. Panels e–g show measured reporter expression, microscopy and flow cytometry; panels a–c show model predictions, not experimental efficacy. RAW 264.7 macrophages and HeLa cells; eGFP mRNA; n=6 for panel e and n=3 for microscopy; 20 µm scale bars.
Xu et al. (2024), Nature Communications, Figure 4. CC BY 4.0. Original figure unchanged. Original article / figure · CC BY 4.0. Unmodified complete original figure; displayed at responsive size.

Laboratory planning

Solution Calculators

The product molecular weight is prefilled when available and remains editable. Confirm solvent compatibility and solubility before preparation.

Mass = concentration × volume × molecular weight

MassConcentrationVolumeMolecular weightg/mol

Enter any three values to calculate the fourth.

C₁V₁ = C₂V₂

C₁mMV₁mLC₂mMV₂mL

Enter any three values to calculate the fourth.

Preparing stock solutions

Quick preparation table

Solvent volumes update from the molecular weight above.

Mass	1 mM	5 mM	10 mM
10 mg	18.1163 mL	3.6233 mL	1.8116 mL
25 mg	45.2907 mL	9.0581 mL	4.5291 mL
50 mg	90.5814 mL	18.1163 mL	9.0581 mL
100 mg	181.1627 mL	36.2325 mL	18.1163 mL
250 mg	452.9068 mL	90.5814 mL	45.2907 mL

Need a different pack size or technical document?

Contact our team with the catalog number and requested quantity.

Handling guidance

Shipping, storage and sampling

How is the lipid shipped, and how should I store it?

We generally ship the neat (undissolved) lipid compound rather than an ethanol solution. The neat lipid is stable during transport with ice packs, and shipments originate from Shanghai. Pure form: store at −20 °C for up to 1 year. Solution shelf life is not established for this product; use a validated solvent and aliquoting procedure. Keep sealed and protected from light. Avoid repeated thaw cycles for best results.

Pure lipid or solution — which should I choose?

Pure lipid is generally more stable during shipping and storage, so we usually recommend the pure form. A solution in ethanol or chloroform can be supplied when required by your workflow. Tell us the intended application, solvent and target concentration so the most suitable format can be confirmed.

How should I measure a small amount of oily or viscous lipid?

Ionizable lipids are often oily liquids or viscous semisolids, so material can be lost during repeated weighing or transfer. For a small pack, dissolve the entire quantity and aliquot it volumetrically. For example, add 1 mL ethanol to 25 mg lipid to prepare a 25 mg/mL stock, then use a pipette to withdraw the required amount. For quantities above 100 mg, direct weighing with an analytical balance may be more practical. Always confirm solvent compatibility and solubility first.

Can you support formulation optimization and scale-up?

Yes. Share the RNA cargo, target tissue, administration route, formulation method and assay plan. Our team can discuss starting molar ratios, N/P ratio and scale-up requirements for research workflows.

What is specific to Lipid R6?

R6 is supplied as an unformulated lipid building block. The reported macrophage data depend on the complete LNP formulation. Its saturated tail scaffold has no ester or disulfide linkage; do not assume the degradability profile of H9. Product-specific long-term stock-solution stability is not established.