LNP Formulation

LNP Formulation

For RNA, siRNA, DNA, peptides

Home » IVT RNA Production Services » Lipid Nanoparticle Packaging for Advanced RNA Delivery

A Novel Drug Delivery Vehicle

GenScript offers lipid nanoparticle (LNP) formulation services to support the delivery of DNA, RNA, siRNA, peptides and other molecules. Our LNP technologies enhance molecular stability, enable efficient cellular uptake, and improve bioavailability—empowering breakthroughs in therapeutic development, gene editing, and functional studies.

To further advance precision, we are excited to introduce two expanded offerings:

Targeted LNP Service – This advanced platform leverages state-of-the-art lipid formulations and targeting ligands to deliver therapeutic payloads directly to specific cells or tissues. By enhancing targeting accuracy, this service maximizes therapeutic efficacy while minimizing off-target effects.

ReadyEdit LNP – Our ReadyEdit solution streamlines delivery of gene editing cargos by offering pre-optimized LNP formulations tailored for high-efficiency CRISPR and RNA payload delivery. It enables researchers to accelerate discovery and functional genomics applications without the complexity of LNP optimization.

Variety of ionizable lipid formulation with high encapsulation efficiency

Targeted LNP Formulations available for specific cells or tissue types

ReadyEdit LNP Formulations with CRISPR RNA solutions

Rush mRNA Synthesis New!

GMP-like mRNA Manufacturing Services

Catalog IVT mRNA, circRNA, saRNA, LNP products

mRNA QC Analysis

GenScript Cap Technology

Circular RNA Synthesis

Self-Amplifying RNA

LNP Formulation

Targeted LNP Formulation

ReadyEdit LNP Formulation

LNP Service Options

Characteristics

Ionizable lipid formulations (MC3-LNP / SM102-LNP/ ALC0315-LNP/LP01-LNP), including novel LNPs

Final concentration can be customized <2 mg/mL

Liquid, ships frozen on dry ice, one time freeze/thaw cycle

Calculate payload needed

QC Testing

Encapsulation Efficiency: >85%

Size Distribution: POI ±20 nm

Polydispersity Index: <0.2

Zeta potential: ± 15 mV

pH: 7.4 ± 0.5

Endotoxin : <4 EU/ml

Size/Scale Options

Load 20 nt ~ 20 kb mRNA

Load 0.1- gram level mRNA

Administration

Intramuscular (I.M.) for animal use only

Intravenous (I.V.) for animal use only

For in vitro studies

Manufacturing Workflow

Our integrated IVT RNA manufacturing workflow streamlines production from gene synthesis to LNP packaging.

Codon/ Ready-to-use UTR designs

Codon optimization for protein expression

Codon optimization with >200 factors screened (patent)

Screened and validated UTR sequences

Gene Synthesis

100 bp – 200 kb gene inserts

TAT as fast as 7 BD to 14 BD

Gene synthesis with Poly(A)-built-in vectors

Cloning/ Plasmid Preparation

Ready-to-use linearized plasmid DNA for IVT

Vectors encoded stable Poly(A) tracts with variance of only +/- 5 nt

mRNA Synthesis

RUO to GMP-like grade

Advanced purification (Oligo dT, dsRNA removal) and variety of QC options

Lipid Nanoparticles Delivery

Generic LNP, Targeted LNP and ReadyEdit LNP (for gene editing)

Load 0.1 mg ~ Gram Level mRNA/circRNA/saRNA/siRNA/ASO/DNA

Load up to 20 kb mRNA

LNP for Different Payloads

mRNA

siRNA

DNA

Peptide

GenScript’s LNP platform demonstrates robust performance with mRNA payloads, showing uniform morphology, low empty-particle rate, high transfection efficiency, and potent in vivo delivery.

GenScript LNPs showed uniform morphology under cryo-EM characterization

GenScript LNPs exhibit a low percentage of empty LNPs (<2%).

GenScript LNPs demonstrate high transfection efficiency.GenScript LNP showed better transfection efficiency than Lipofectamine

GenScript LNPs showed strong in vivo signal 8 hours after IV (left) or IM (right) injection in mice

GenScript siRNA-LNP Demonstrates Effective Gene Silencing

LNP 1: EGFP mRNA-LNP (SM102)

LNP 2: EGFP siRNA-LNP (MC3)

LNP 3: Scramble siRNA-LNP (MC3)

When the EGFP-mRNA-LNP (LNP 1) were co-transfected with EGFP-siRNA-LNP (LNP 2), there is no EGFP expression observed (LNP 1 + LNP 2), indicating the excellent gene silencing effects of siRNA LNP; Scramble-siRNA-LNP (LNP 3) was served as positive control (LNP 1 + LNP 3)

LNPs for Efficient Plasmid DNA Delivery

SM102-NLS formulation

Incorporation of the NLS peptide into the general SM102 LNP formulation significantly enhances plasmid DNA delivery efficiency.

C12-200 formulation

The C12-200 LNP formulation exhibits significantly higher plasmid DNA delivery efficiency compared with the general SM102 formulation.

Peptide encapsulation with LNP

FITC-labeled peptide was either directly incubated with A549 cells or encapsulated in LNPs for delivery. Fluorescence intensity and cell viability were analyzed 24 hours post-transfection. LNP encapsulation markedly enhanced peptide delivery efficiency with minimal cytotoxicity.

Novel LNPs

GenScript is introducing novel LNP formulations featuring unique lipid compositions that deliver strong in vitro and in vivo performance, comparable to or exceeding benchmark systems like SM102 and ALC0315. These next-generation LNPs also avoid dependence on conventional benchmark lipids and show promising tissue/cell targeting potential, offering powerful new options for mRNA delivery, vaccines, gene editing, and cell therapy.

CXM-2

CX108

CX175

SM-CX712

mRNA-LNP for hCCR9 antibody production. We designed hCCR9 mRNA sequence and encapsulated the mRNA into different LNP formulations, and the results showed the mRNA-LNPs could successfully induce corresponding antibody of hCCR9 protein in mice. 1WP3: 1 week post 3rd immunization; 7WP3: 7 weeks post 3rd immunization; 11WP3: 11 weeks post 3rd immunization.

For in vitro test, HEK293T Cells were plated in 6-well plate at 300,000 cells per well. Cells were transfected with 2.5ug of mRNA-LNP per well. 48h after transfection, the expression of hCCR9 protein was detected using flow cytometry analysis with primary antibody against CCR9 and fluorescent secondary antibody.

For in vivo test, mice were intramuscularly injected with hCCR9 mRNA encapsulated in SM102, CXM-2, or ALC-0315 LNPs (0.5 mg/kg), without adjuvants. Mice received multiple immunizations, and serum samples were collected at weeks 1, 7, and 11 after the third immunization. To assess the CCR9-specific antibody response, a hCCR9 overexpressing CHO-K1 stable cell line was used as the screening material. Cells were incubated with diluted mouse serum, followed by staining with a fluorescently labeled secondary antibody, and analyzed by flow cytometry.

CXM-2 is also a promising candidate for gene editing. See ReadyEdit LNPs for prime editing application

CX108 LNP exhibited comparable in vivo performance to the benchmark SM102 LNP, and demonstrated enhanced expression in primary T cells after CD3 antibody conjugation, highlighting its potential for in vivo CAR-T applications.

CX175 LNP exhibited comparable in vivo performance to the benchmark SM102 LNP, and demonstrated enhanced expression in primary T cells after CD3 antibody conjugation, highlighting its potential for in vivo CAR-T applications.

SM-CX712 LNP can enhance RNA’s distribution to muscle, and reduce its expression in liver by IM injection

Popular off-the-shelf mRNA_LNP catalogs available now!

Try our catalog mRNA_LNP products, including SM102, LP01, and ALC0315 LNP formulations loaded with mRNA expressing eGFP, F-Luciferase or eSpCas9, delivered in just 5 days!

“Not sure which T-cell targeted LNP fits your application? Check our LNP selector tool for guidance.”

Quality Control and Specification

Appearance

Visual Inspect

Clear and free of foreign particles​

Final Concentration

RiboGreen assay

0.05 – 0.4 mg/mL

Encapsulation Efficiency

> 85%

Encapsulated RNA Integrity

Bioanalyzer

> 75%

Particle size

Dynamic light scattering

MC3-LNP 80-110 nm SM102-LNP 65-125 nm LP01-LNP 65-125 nm ALC0315-LNP 50-100 nm

Poly Dispersity Index

< 0.2

Zeta Potential

Zetasizer by dynamic light scattering

Zeta potential varies with different LNP formulations

pH​

pH paper

7.4 ± 0.5​

Endotoxin​

Quantitative

<4 EU/ml

Bioburden​

Direct inoculation

No Growth after 72 hrs

Lipid Composition

LC-CAD

as detected

Upon Request

Antibody conjugation efficiency

Bradford assay

Case Studies

Espcas9 mRNA/sgRNA targeting TARC (GenScript) were formulated in LP01-LNP formulation at 1:1 mass ratio achieved 97% editing efficiency, comparing to 61% by lipofectamine.

2.4 ug of RNA/LNP formulation were incubated with HEK293T cells, cell were lysed at day 3 and day 5 for PCR and sanger sequencing.

Transfection efficiency was compared by delivering eGFP mRNA (100% N1-methyl-pseU modified, GenScript) into Jurkat and THP-1 immune cells using SM102-LNP (GenScript), Lipofectamine™ MessengerMAX™ (ThermoFisher Scientific) and TransIT® (Mirus). 100ng of mRNA were transfected into cells in 24 well plates. Starvation medium (OptiMEM) was used for lipofectamine and TransIT per the manufacturer’s instruction, and complete medium was used for LNP. The expression of eGFP was measured by flow cytometry after 48 hours.

GS-MC3 LNP formulation has strong mRNA expression

GS-MC3 LNP as generic formulation for customers’ mRNA screening project

In vivo delivery efficiency of four different LNP formulations was compared by delivering Fluc mRNA (100% N1-methyl-pseU modified, GenScript) into Balb-C mice via IM injection at a dose of 0.25mg/kg. The expression of Fluc mRNA was measured by whole-body bioluminescence imaging.

Fluc mRNA delivered by MC3-LNP showed the highest expression level after 8 and 48 hours by imaging at both Dorsal and Ventral pose of mice. To evaluate the biodistribution profile of different formulations, the heart, liver, lung, spleen, kidney, and brain of the mice were collected and imaged after 48 hours, MC3 -LNP formulation showed the strongest liver accumulation compared to others after 48 hours.

Both LNP formulations are safe for IV injection

SM102 has stronger liver accumulation among the two tested formulations

In vivo delivery efficiency of two different LNP formulations was compared by delivering Fluc mRNA (100% N1-methyl-pseU modified, GenScript) into Balb-C mice via IV injection at a dose of 0.3mg/kg. The expression of Fluc mRNA was measured by whole-body bioluminescence imaging.

In imaging analysis, Fluc-mRNA delivered by SM102-LNP showed higher expression efficiency than MC3 after 8 and 48 hours. To evaluate the biodistribution profile of different formulations, heart, liver, lung, spleen, kidney, and brain of the mice were collected and imaged after 48 hours, SM102 -LNP showed stronger liver accumulation compared to MC3-LNP after 48 hours. MC3-LNP showed stronger spleen accumulation after 48 hrs. Neither formulation caused significant body weight loss during the experiment period for 3 days.

Resources

LNP Case Study Report

Case studies demonstrating encapsulation and delivery efficiency of GenScript’s new LNP formulations in cell models, and mouse models via both IM and IV.

Questions On Storage And Usage Guidelines_mRNA, saRNA and LNP

mRNA LNP in vitro Cell Transfection

FAQs

Lipid nanoparticles (LNPs) are natural or synthetic molecules that can self-assemble into a spherical structure. LNPs are typically composed of lipid layer, which forms a shell around an inner compartment that can be used to deliver drugs or other therapeutic agents. LNPs have become increasingly popular as a drug delivery system due to their ability to protect therapeutic agents from degradation and improve their bioavailability. They can also be designed to target specific cells or tissues, allowing for more precise delivery of drugs. LNPs have been used in various applications, including the delivery of RNA-based therapeutics such as mRNA vaccines. The lipid layer of LNPs can fuse with the cell membrane, allowing the encapsulated RNA to enter the cell and exert its therapeutic effect. LNPs have also been investigated as a potential delivery system for other types of drugs, including small molecules and proteins.

We accept various antibody formats for targeted LNP conjugation, including:

Full-length antibodies (IgG)

scFv (single-chain variable fragments)

Fab fragments

VHH (nanobodies)

Other antibody formats

If you have questions about a specific antibody format, please contact our technical team to discuss compatibility.

Our LNP service encapsulates 20nt - 10knt RNA.

MC3 LNP is formulated with the main ionizable lipid MC3, which was used for siRNA LNP formulation, it is less effective in mRNA delivery compared to SM102 and ALC0315 formulation.

SM102 LNP was used in COVID vaccine, it has good delivery efficiency for mRNA, and accumulates in the liver.

ALC0315 LNP was used in COVID vaccine, it has good delivery efficiency for mRNA and CRISPR (mRNA +sgRNA), and accumulates in the liver.

LP01 LNP was tested for its efficienct delivery of CRISPR (mRNA +sgRNA).

All of these LNP formulation (MC3 / SM102/ ALC0315 or LP01) are not active targeting formulations, so they tend to accumulate in the liver instead of targeting to specific tissues. However, if you need organ-specific LNP, we can offer customized formulation per the customer's request. Please reach out to our technical support team for details.

mRNA LNP In Vitro CellTransfection Protocol GenScrip

We recommend SM102 and ALC0315 LNPs for mRNA, these two has shown great efficiency in delivery mRNA in vivo. You can acquire off-the-shelf LNP loaded with mRNA coding for marker gene to perform initial studies for their project needs.

MC3-LNP has been successfully used in siRNA delivery previously.

Yes, We can formulate multiple guide RNA and Cas9 mRNA into one LNP formulation. GenScript also provides sgRNA synthesis service up to 160nt long and customized Cas9 virants mRNA production.

Yes, we do. Please reach out to our technical support team for details.

We use microfluidic device and chip to prepare LNP.

The final encapsulation efficiency is >90%. However, we expect ~50% payload loss during the encapsulation process. For example, 2mg payload input could expect 1mg encapsulated, with a variance of ±10% in final amount encapsulated.

We suggest to order 200ug of mRNA for encapsulation.

Typical concentration we provide is 0.1-0.4 mg/ml. The highest concentration we can provide is 2mg/mL.

For the LNP final buffer solution, we use Tris buffer which will enable longer-term stability compared with PBS, according to the research results from Moderna. We also offer the option of using PBS with sucrose or Tris with sucrose as the final buffer for LNP. Sucrose is used as a cryoprotectant. Default buffer is PBS with sucrose.

We suggest to thaw LNP and keep at 4°C after thaw for up to 1 month. Dilute with PBS or tris based on your final buffer.

If you plan to store LNP for longer than 3 months, it is recommended to add a cryoprotectant. GenScript will ship LNP in default buffer PBS with sucrose on dry ice. We recommend to store LNP at -80°C upon receipt until use. Avoid freeze-thaw cycles. Suggest to thaw on the day of use, otherwise keep your thawed LNP at 4°C for up to 1 month.

The LNP should be stable for at least 3 months if stored properly at -80°C upon receival and avoiding repeated freezing and thawing cycles. The amount of freeze/thaw cycles depends on the mRNA length. For 1-2kb, we suggest not to freeze/thaw more than 2 times. For 2-5kb, we suggest no more than once freeze/thaw. If you need to thaw the LNP, it is suggested to thaw them on ice and keep the thawed formulation at 4°C.

Plate cells and incubate overnight to 24 hours. Cells grown and transfected in complete media (DMEM +10% FBS) has higher expression than reduced serum medium.

Calculate mRNA and LNP dose needed. Add LNP directly to cells incubated in complete media.

Incubate for expression and analysis. For eGFP expression and analysis on plate reader, we recommend using low fourescent background media such as Flourobrite® with 10% FBS, 1X GlutaMax® and 1X sodium pyruvate.

Same protocol can be used for adherent and immune cell lines as well.

Additional mRNA Offerings

Custom mRNA

High-quality custom mRNA production via our proprietary IVT RNA manufacturing workflow.

Catalog IVT RNA

Our off-the-shelf mRNA is optimized with 5’ cap and polyA tails that is ready to use for your research needs

Circular RNA

Circular RNA offers improved stability and longer expression duration.

Plasmid DNA Linearization

High quality linearized DNA plasmid for better quality and consistency of your mRNA production

Get in Touch with GenScript Lipid Nanoparticle Formulation

REQUEST A QUOTE

EMAIL

[email protected]

PHONE

1-877-436-7274

ONLINE FORM

Online Quote Submission

FAX

1-732-210-0262