Cat. No.: HY-138170

ALC-0315

43 Cited Publications

Customer Review

Based on 43 publication(s) in Google Scholar

ALC-0315 is an ionisable aminolipid that is responsible for mRNA compaction and aids mRNA cellular delivery and its cytoplasmic release through suspected endosomal destabilization. ALC-0315 can be used to form lipid nanoparticle (LNP) delivery vehicles. Lipid-Nanoparticles have been used in the research of mRNA COVID-19 vaccine.

For research use only. We do not sell to patients.

Purity: 99.90%
CAS No.: 2036272-55-4
Formula: C₄₈H₉₅NO₅
Molecular Weight:766.27

Storage:

4°C, protect from light

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

ALC-0315 Chemical Structure

CAS No.: 2036272-55-4

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Biological Activity
- Description
- In Vitro
Chemical Information
Publications (43)
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

In Vitro

Preparation of Lipid Nanoparticles

Here we provide lipid molar ratios for LNPs in FDA-approved BNT162b2 (a COVID-19 mRNA vaccine). The molar ratio of lipids in this formulation is ALC-0315 : DSPC : Cholesterol : ALC-0159 = 46.3 : 9.4 : 42.7 : 1.6, and RNA to lipid weight ratio is 0.05 (wt/wt)^[1].

A. Lipid Mixture Preparation

1. Dissolve lipids in ethanol and prepare 10 mg/m stock solutions. The lipid stock solutions can be stored at 20°C for later use.

Note 1: The ionizable lipid is usually a liquid. Due to the viscosity, it should always be weighed rather than relying on the autopipette volume.

Note 2: Cholesterol in solution should be kept warm (>37°C) to maintain fluidity. Transfer the cholesterol solution promptly to avoid cooling.

2. Prepare the lipid mixture solution as described. For each mL of lipid mixture add the following: 560 μL of 10mg/mL ALC-0315 (HY-138170), 261 μL of 10mg/mL Cholesterol (HY-N0322), 117 μL of 10mg/mL DSPC (HY-W040193), and 62 μL of ALC-0159 (HY-138300). Mix the solutions thoroμghly to achieve a clear solution. This mixture contains 10 mg of total lipid.

Note 3: The choice of lipids and ratios may be changed as desired and this will affect the LNP properties (size, polydispersity, and efficacy) and the amount of mRNA required.

B. mRNA Preparation

1. Prepare a 166.7 μg/mL mRNA solution with 100 mM pH 5 sodium acetate buffer.

Note 4: The lipid:mRNA weight ratio influences the encapsulation efficiency. Other weight ratios may be prepared as alternative formulations and should be adjusted accordingly by user.

C. Mixing

There are three commonly used methods to achieve rapid mixing of the solutions: the pipette mixing method, the vortex mixing method, and the microfluidic mixing method. All these mixing methods can be used for various applications.

It is important to note that pipette mixing method and vortex mixing method may yield more heterogeneous LNPs with lower encapsulation efficiencies and is prone to variability. Microfluidic devices enable rapid mixing in a highly controllable, reproducible manner that achieves homogeneous LNPs and high encapsulation efficiency. Within these devices, the ethanolic lipid mixture and aqueous solution are rapidly combined in individual streams. LNPs are formed as the two streams mix and are then collected into a single collection tube.

1. Pipette Mixing Method:

1.1. Pipette 3 mL of the mRNA solution and quickly add it into 1 mL of the lipid mixture solution (A 1:3 ratio of ethanolic lipid mixture to aqueous buffer is generally used.) Pipette up and down rapidly for 20-30 seconds.

1.2. Incubate the resulting solution at room temperature for up to 15 minutes.

1.3. After mixing, the LNPs were dialyzed against PBS (pH 7.4) for 2 h, sterile filtered using 0.2 μm filters, and stored at 4°C.

2. Vortex Mixing Method:

1.1. Vortex 3 mL of mRNA solution at a moderate speed on the vortex mixer. Then, Quickly add 1 mL of the lipid mixture solution into the vortexing solution (A 1:3 ratio of ethanolic lipid mixture to aqueous buffer is generally used.). Continue vortexing the resulting dispersion for another 20-30 seconds.

1.2. Incubate the resulting solution at room temperature for up to 15 minutes.

1.3. After mixing, the LNPs were dialyzed against PBS (pH 7.4) for 2 h, sterile filtered using 0.2 μm filters, and stored at 4°C.

3. Microfluidic Mixing Method:

1.1 The 3 mL of mRNA buffer solution and 1 mL of the lipid mixture solution were mixed at a total flow rate of 12 mL/min in a microfluidic device (A 1:3 ratio of ethanolic lipid mixture to aqueous buffer is generally used.).

Note 5: Parameters such as the flow rate ratio and total flow rate can be altered to fine-tune LNPs.

1.2. After mixing, the LNPs were dialyzed against PBS (pH 7.4) for 2 h, sterile filtered using 0.2 μm filters, and stored at 4°C.

Reference

1. Curr Issues Mol Biol. 2022 Oct 19;44(10):5013-5027.

2. Curr Protoc. 2023;3(9):e898.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Chemical Information

CAS No. 2036272-55-4
Appearance Liquid (Density: 0.919±0.06 g/cm³)
Molecular Weight 766.27
Formula C₄₈H₉₅NO₅
Color Colorless to light yellow
SMILES

OCCCCN(CCCCCCOC(C(CCCCCC)CCCCCCCC)=O)CCCCCCOC(C(CCCCCC)CCCCCCCC)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, protect from light

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Publications (43)

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Journal Impact Factor

Science

Single intramuscular injection of self-amplifying RNA of Nppa to treat myocardial infarction. [Abstract]

2026 Mar 5;391(6789):edau9394. PMID: 41785353
Nat Nanotechnol

A disease-severity-responsive nanoparticle enables potent ghrelin messenger RNA therapy in osteoarthritis. [Abstract]

2026 Jan 14. PMID: 41535382
Mol Cancer

Lipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity. [Abstract]

2025 Jan 13;24(1):12. PMID: 39806486
Adv Mater

Resolving the mRNA Encapsulation-Release Trade-off via Compensatory Forces in Engineered Ionizable Lipids. [Abstract]

2025 Nov 16:e12235. PMID: 41243603
Cell Host Microbe

A CLOCK-targeting lncRNA induces trained immunity against tuberculosis. [Abstract]

2025 Dec 30:S1931-3128(25)00521-9. PMID: 41475336
ACS Nano

Lipid Nanoparticle with 1,2-Di-O-octadecenyl-3-trimethylammonium-propane as a Component Lipid Confers Potent Responses of Th1 Cells and Antibody against Vaccine Antigen. [Abstract]

2024 Jul 2;18(26):16589-16609. PMID: 38885198
ACS Nano

Mesoscopic Structure of Lipid Nanoparticle Formulations for mRNA Drug Delivery: Comirnaty and Drug-Free Dispersions. [Abstract]

2024 Apr 2;18(13):9746-9764. PMID: 38514237
ACS Nano

Enhanced Local Delivery of Engineered IL-2 mRNA by Porous Silica Nanoparticles to Promote Effective Antitumor Immunity. [Abstract]

2023 Sep 12;17(17):17554-17567. PMID: 37643221
Nat Commun

Impact of pre-existing anti-replicase immunity on the efficacy of self-amplifying mRNA vaccines. [Abstract]

2025 Dec 6;17(1):278. PMID: 41353442
Adv Sci (Weinh)

A Single-Dose mRNA Vaccine Employing Porous Silica Nanoparticles Induces Robust Immune Responses Against the Zika Virus. [Abstract]

2024 Jul 15:e2404590. PMID: 39010673
J Nanobiotechnology

Spleen-targeted NeoPol-mL242 mRNA vaccine induces robust T-cell responses in a hepatocellular carcinoma model. [Abstract]

2025 Sep 2;23(1):602. PMID: 40898321
J Control Release

Lipid nanoparticles containing zwitterionic lipids versatilely enhance the efficiency of mRNA delivery. [Abstract]

2026 Feb 8:392:114709. PMID: 41666942
J Control Release

Delivery of Itgb1-siRNA by triptolide-modified and anti-Flt1 peptide-guided ionizable cationic LNPs for targeted therapy of corneal neovascularization. [Abstract]

2025 May 3:113811. PMID: 40324532
J Control Release

Direct structural investigation of pH responsiveness in mRNA lipid nanoparticles: Refining paradigms. [Abstract]

2025 May 20:113848. PMID: 40404049
J Control Release

Splenic B cell-targeting lipid nanoparticles for safe and effective mRNA vaccine delivery. [Abstract]

2025 Apr 3:113687. PMID: 40187650
J Colloid Interface Sci

The vast majority of nucleic acid-loaded lipid nanoparticles contain cargo. [Abstract]

2024 Jun 23:674:139-144. PMID: 38925059
Adv Healthc Mater

Admixing of mRNA with Pre-Formed Lipid Nanoparticles Containing a Slightly-Cationic Ionizable Lipid Allows for Efficient mRNA Transfection In Vitro and In Vivo. [Abstract]

2025 Jun 25:e2501788. PMID: 40557541
Small Methods

Cholesterol-Derived Mannosylated Polypeptide-Formed Lipid Nanoparticles for Efficient in Vivo mRNA Delivery. [Abstract]

2025 Apr 21:e2401712. PMID: 40256901
EMBO Mol Med

LILRB1-HLA-G axis defines a checkpoint driving natural killer cell exhaustion in tuberculosis. [Abstract]

2024 Aug;16(8):1755-1790. PMID: 39030302
ACS Appl Mater Interfaces

Size-Controllable and Monodispersed Lipid Nanoparticle Production with High mRNA Delivery Efficiency Using 3D-Printed Ring Micromixers. [Abstract]

2024 Sep 4;16(35):46044-46052. PMID: 39103250
NPJ Vaccines

A self-amplifying mRNA vaccine expressing PRV gD induces robust immunity against virulent mutants. [Abstract]

2025 Aug 14;10(1):193. PMID: 40813770
NPJ Vaccines

Immunogenicity and biodistribution of lipid nanoparticle formulated self-amplifying mRNA vaccines against H5 avian influenza. [Abstract]

2024 Aug 3;9(1):138. PMID: 39097672
Mol Ther Nucleic Acids

A transferable SARS-CoV-2 IRES module enables dual translation initiation for enhanced antigen expression in COVID-19 mRNA vaccines. [Abstract]

2026 Mar 5;37(2):102886. PMID: 41883582
Mol Ther Nucleic Acids

A novel bispecific siRNA concept: Efficient dual knockdown of YAP1 and WWTR1 with a single guide strand. [Abstract]

2025 Nov 10;36(4):102768. PMID: 41341748
Pharmaceutics

Freeze-Drying in Sucrose Followed by Cryomilling Enables the Formulation of sa-mRNA-LNP Powders for Inhalation. [Abstract]

2026 Jan 18;18(1):121. PMID: 41599228
Biomacromolecules

Replacing PEG-Lipid with Amphiphilic Polycarbonates in mRNA-Loaded Lipid Nanoparticles: Impact of Polycarbonate Structure on Physicochemical and Transfection Properties. [Abstract]

2025 Jun 9;26(6):3563-3575. PMID: 40347133
Vet Q

Influence of the administration route and dose on the expression and antibody responses of a reporter and avian influenza self-amplifying mRNA vaccine in poultry. [Abstract]

2026 Dec;46(1):2603307. PMID: 41496565
ACS Appl Bio Mater

Optimizing Transfection Efficiency in CAR-T Cell Manufacturing through Multiple Administrations of Lipid-Based Nanoparticles. [Abstract]

2024 May 22. PMID: 38775109
Nanomedicine

Quantitative analysis of mRNA-lipid nanoparticle stability in human plasma and serum by size-exclusion chromatography coupled with dual-angle light scattering. [Abstract]

2024 Jun:58:102745. PMID: 38499167
Eur J Pharm Biopharm

Interactions between mRNA lipid nanoparticles and immune cells in fresh human whole blood. [Abstract]

2026 Jun 9:115146. PMID: 42264006
J Gen Virol

Broadly neutralizing monoclonal antibodies derived from mRNA LNP immunization exhibit potent neutralizing ability against JN.1, KP.3.1.1 and XEC new Omicron variants. [Abstract]

2026 Apr;107(4). PMID: 42030071
J Chromatogr A

A platform method for simultaneous quantification of lipid and nucleic acid components in lipid nanoparticles. [Abstract]

2025 Apr 12:1746:465788. PMID: 39987694
Membranes

Mesoscopic Structure of Lipid Nanoparticles Studied by Small-Angle X-Ray Scattering: A Spherical Core-Triple Shell Model Analysis. [Abstract]

2025 May 16;15(5):153. PMID: 40422763
Vaccines

Immunogenic Comparison of Nucleic Acid-Based Vaccines Administered by Pyro-Drive Jet Injector. [Abstract]

2024 Jul 9;12(7):757. PMID: 39066395
Immunol Cell Biol

Age-related differences in mRNA vaccine immunogenicity and adjuvancy. [Abstract]

2026 Mar 12. PMID: 41819108
Electrophoresis

Capillary-Based Physicochemical Characterization of Lipid Nanoparticles. [Abstract]

2025 Sep 28. PMID: 41015920
SSRN

2026 Jun 18.
bioRxiv

2026 May 4.
bioRxiv

2025 Jun 17.
bioRxiv

2025 January 21.
Research Square Preprint

2023 Sep 12.
Research Square Preprint

2023 Aug 3.
bioRxiv

2023 Jun 10.

Solvent & Solubility

In Vitro:

Ethanol : 100 mg/mL (130.50 mM; Need ultrasonic)

DMSO : 50 mg/mL (65.25 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.3050 mL

6.5251 mL

13.0502 mL

5 mM

0.2610 mL

1.3050 mL

2.6100 mL

10 mM

0.1305 mL

0.6525 mL

1.3050 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (3.26 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: 2.5 mg/mL (3.26 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (3.26 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (273 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Moghimi SM. Allergic Reactions and Anaphylaxis to LNP-Based COVID-19 Vaccines. Mol Ther. 2021;29(3):898-900. [Content Brief]

[2]. Ferraresso F, Strilchuk AW, Juang LJ, Poole LG, Luyendyk JP, Kastrup CJ. Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells. Mol Pharm. 2022;19(7):2175-2182. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO / Ethanol	1 mM	1.3050 mL	6.5251 mL	13.0502 mL	32.6256 mL
	5 mM	0.2610 mL	1.3050 mL	2.6100 mL	6.5251 mL
	10 mM	0.1305 mL	0.6525 mL	1.3050 mL	3.2626 mL
	15 mM	0.0870 mL	0.4350 mL	0.8700 mL	2.1750 mL
	20 mM	0.0653 mL	0.3263 mL	0.6525 mL	1.6313 mL
	25 mM	0.0522 mL	0.2610 mL	0.5220 mL	1.3050 mL
	30 mM	0.0435 mL	0.2175 mL	0.4350 mL	1.0875 mL
	40 mM	0.0326 mL	0.1631 mL	0.3263 mL	0.8156 mL
	50 mM	0.0261 mL	0.1305 mL	0.2610 mL	0.6525 mL
	60 mM	0.0218 mL	0.1088 mL	0.2175 mL	0.5438 mL
Ethanol	80 mM	0.0163 mL	0.0816 mL	0.1631 mL	0.4078 mL
Ethanol	100 mM	0.0131 mL	0.0653 mL	0.1305 mL	0.3263 mL

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ALC-0315

Anti-Infection Compound Library

Metabolism/Protease Compound Library

Lipid Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Liposome Library

Ionizable Lipid Compound Library

Publications Citing Use of MedChemExpress (MCE) ALC-0315

Biological Activity

Chemical Information

Publications (43)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

ALC-0315

Anti-Infection Compound Library

Metabolism/Protease Compound Library

Lipid Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Liposome Library

Ionizable Lipid Compound Library

Publications Citing Use of MedChemExpress (MCE) ALC-0315

Biological Activity

Chemical Information

Publications (43)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

ALC-0315 Related Classifications

Cat. No.: HY-138170