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CAT. NO. DC67539Featured

Lipid CS22021

Research highlights

Three-component LNP formulationNo added free cholesterolLocalized IM expression (abstract)Preclinical mRNA vaccine research

Pack size & price

USD

Total$800

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Ships from ShanghaiIce-pack transportPure lipid recommended

Product overview

Description & Application

CS22021 is a novel, synthetically engineered ionizable sterol lipid (ISL) developed by CanSino, specifically designed for advanced mRNA delivery via lipid nanoparticles (LNPs). Its core innovation lies in its unique molecular architecture, which integrates a cholesterol moiety directly conjugated to a branched aliphatic tail (derived from ALC-0315) and a hydrophilic headgroup containing tertiary amines. This bifunctional design allows CS22021 to simultaneously fulfill the roles of both the ionizable lipid (for mRNA binding/encapsulation and endosomal escape) and the structural cholesterol component within LNPs. Consequently, CS22021 enables the formulation of highly efficient three-component LNPs (ISL-3C-LNPs), eliminating the need for free cholesterol, using only itself, the phospholipid DOPE (crucial for forming stable, uniform nanoparticles without defects), and a PEGylated lipid. When formulated into LNPs and administered intramuscularly, CS22021 demonstrates a critical property: it achieves localized mRNA expression predominantly at the injection site, significantly minimizing off-target delivery (especially to the liver/spleen) and associated systemic toxicity. Furthermore, mRNA vaccines delivered by CS22021-based LNPs elicit robust and balanced immune responses, including strong antigen-specific IgG antibodies and, notably, a significantly enhanced CD8+ T cell response compared to conventional four-component LNPs. This combination of efficient mRNA encapsulation/delivery, localized expression for improved safety, and potent induction of cellular immunity, particularly CD8+ T cells, positions CS22021 as a highly promising lipid platform, especially for next-generation mRNA vaccine applications like cancer immunotherapy.

CAS No.	Not available
Chemical Name	Lipid CS22021
Synonyms	Lipid-CS22021, CS22021
SMILES	CCCCCCCCC(CCCCCC)C(=O)OCCCCCCN(CCCN1C=CN=C1)CCOC(=O)O[C@H]1CC[C@@]2(C)C(C=C[C@@H]3[C@@H]2CC[C@@]2(C)[C@H]3CC[C@@H]2[C@H](C)CCCC(C)C)C1
Formula	C58H101O5N3
M.Wt	920.46
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	Wang Z, Yan Z, Yan S, et al. Ionizable Sterol Lipid-Based Three-Component Lipid Nanoparticles for Localized Delivery of mRNA Vaccine with Stronger Cellular Immune Responses. ACS Applied Materials & Interfaces. 2025;17(25):36377-36386.

Literature-reported formulation composition

Component	Reported component ratio	Role
CS22021	49.25	Ionizable lipid
DOPE	49.25	Helper phospholipid
M-DMG-PEG2K	1.5	PEG lipid
Reported ratio sum	100	Original ratio retained

Formulation calculator unavailable. The SI prints the component ratio without defining its molar-versus-mass basis or the exact molecular weight of M-DMG-PEG2K. Confirm both before calculating component weights. Obtain and verify the complete composition and component molecular weights before planning component quantities.

N/P ratio8

CargoLuciferase mRNA reporter; gE vaccine cargo is listed separately in Table S2.

Administration routeIV reporter assay (SI Fig. S5); IM localization (abstract only).

DoseIV: 5 micrograms mRNA/mouse. IM dose not available in supplied SI/abstract.

Animal modelIV: male BALB/c mice, 6-8 weeks, n=3.

Formulation processNot specified in supplied SI or abstract.

Literature-reported performance for the cited formulation

Literature-reportedParticle size83.13 nmSI Table S1: CS22021/DOPE/M-DMG-PEG2K formulationSI Table S1, p. S3; Luc-CS22021 in Table S2, p. S7

Literature-reportedPolydispersity index0.091SI Table S1: CS22021/DOPE/M-DMG-PEG2K formulationSI Table S1, p. S3; Table S2, p. S7

Literature-reportedmRNA encapsulation efficiency89%SI Table S1: CS22021/DOPE/M-DMG-PEG2K formulationSI Table S1, p. S3; Table S2, p. S7

Literature-reportedZeta potential-4.77 mVSI Table S1: CS22021/DOPE/M-DMG-PEG2K formulationSI Table S1, p. S3; Table S2, p. S7

Literature-reportedApparent LNP pKa (TNS)5.804Formulated nanoparticles; not neat-lipid pKa · ALC-0315-based 4C-LNP: 6.267SI Fig. S6, p. S9

Helper-phospholipid comparison

CS22021 / helper / M-DMG-PEG2K	N/P	Size (nm)	PDI	EE (%)	Zeta (mV)
DSPC: 49.25 : 49.25 : 1.5	8	63.41	0.13	87	+1.14
DOPE: 49.25 : 49.25 : 1.5	8	83.13	0.091	89	-4.77

SI Table S1, p. S3. Original ratios are retained. Neither variant includes added free cholesterol.

Cargo-specific LNP properties for animal studies

SI sample name	Size (nm)	PDI	EE (%)	Zeta (mV)
Luc-CS22021	83.13	0.091	89	-4.77
Luc-ALC-0315	78.16	0.088	93	-7.18
gE-CS22021	102.6	0.096	97	-7.94
gE-ALC-0315	75.92	0.069	92	-3.46

SI Table S2, p. S7. Values refer to the named LNP/cargo samples, not the supplied neat lipid. gE and luciferase results are kept separate.

Additional reported findings

DOPE versus DSPC in Hep3B cells

The plotted luciferase signal is higher for the DOPE formulation than the DSPC formulation. Exact numerical means and a statistical comparison are not printed.

Luciferase assay; mean with SEM; qualitative reading of the figure. · SI Fig. S3, p. S5

Cell-line-dependent transfection

CS22021 shows higher plotted luciferase signals in HeLa and A549, substantially lower signal in HEK293T, and similar signal in Hep3B relative to ALC-0315. This does not support a claim of universally superior transfection.

Mean with SEM; exact means are not digitized. The caption has HEK203T, whereas the graph labels HEK293T. · SI Fig. S4, p. S6

IV reporter biodistribution

Whole-animal imaging was performed at 6, 12 and 24 h; organs were imaged at 24 h. The plots show lower whole-animal and liver/spleen expression for CS22021 than ALC-0315 under this IV condition. This result does not establish IM injection-site localization.

5 micrograms mRNA/mouse; male BALB/c, 6-8 weeks; n=3; qualitative graph comparison. · SI Fig. S5, p. S8

Localized IM expression and immune responses

The indexed main-article abstract reports localized mRNA expression at the IM injection site, robust humoral and cellular responses to a VZV mRNA vaccine, and significantly higher CD8+ T-cell responses versus a conventional LNP. It provides no effect size or immunization schedule.

Abstract-level qualitative findings; cancer-vaccine use is proposed as a potential application, not demonstrated tumor efficacy in the available evidence. · Main-article abstract, PMID 40503610

Cell viability and safety evidence

HEK293T CCK-8 viability is plotted near the control level under the tested conditions. Rat serum ALT/AST measurements are shown for days 18 and 24. The supplied SI lacks the full rat dosing regimen and a numerical statistical safety comparison; no clinical safety or no-toxicity claim is made.

SI Fig. S7: CCK-8 at 24 h after exposure. Fig. S9 illustrates a 0-4 muscle inflammation scoring scale, not treatment-group outcome scores. · SI Fig. S7, p. S10; Fig. S8, p. S11; Fig. S9, p. S12

Literature Data DisclaimerAll formulation parameters and performance values shown in this section are derived from the cited publication and are provided for reference only. These results were obtained using the specific materials, formulation process, cargo, dose, analytical method, model and administration route described in that study. Unless otherwise stated, the data were not generated or independently verified by DC Chemicals. DC Chemicals supplies the lipid compound only and does not guarantee that customers will reproduce the reported LNP properties or biological performance.

The administration route shown above was used in the cited study and is not a clinical-use instruction or recommendation by DC Chemicals.

Cited literature for this formulation and performance datasetWang Z, Yan Z, Yan S, et al. Ionizable Sterol Lipid-Based Three-Component Lipid Nanoparticles for Localized Delivery of mRNA Vaccine with Stronger Cellular Immune Responses. ACS Applied Materials & Interfaces. 2025;17(25):36377-36386. DOI: 10.1021/acsami.5c04597
Numerical data: supplied 16-page SI, Tables S1-S2 and Figs. S5-S6. IM localization and immune-response claims: indexed abstract only. Full article methods were not accessible.

Publisher Supporting Information · PubMed abstract

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	10.8641 mL	2.1728 mL	1.0864 mL
25 mg	27.1603 mL	5.4321 mL	2.7160 mL
50 mg	54.3207 mL	10.8641 mL	5.4321 mL
100 mg	108.6413 mL	21.7283 mL	10.8641 mL
250 mg	271.6033 mL	54.3207 mL	27.1603 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. In solvent: store at −80 °C for up to 6 months or at −20 °C for up to 1 month. 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.

Lipid CS22021

Pack size & price

Description & Application

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