At LipExoGen, LipExoGen harness the transformative power of mRNA LNP technology to advance therapeutic development. Our comprehensive services are designed to meet the unique needs of researchers, pharmaceutical companies, and government agencies, providing tailored solutions for mRNA delivery. Our team's expertise spans the customization of LNP formulations for precise targeting, stability, and efficient mRNA encapsulation, catering to diverse research and development initiatives. With state-of-the-art technology and unparalleled expertise, LipExoGen delivers LNPs optimized for size, charge, and surface properties, ensuring superior performance and reproducibility.
LipExoGen offers extensive capabilities to encapsulate a variety of cargos such as mRNA, siRNA, sgRNA, miRNA, ASO, ODN CpG, and DNA. Our surface modification options include monoclonal antibodies, nanobodies, proteins, cytokines, peptides like cRGD, aptamers, glycosylation, and small molecule ligands for specific targeting. LipExoGen is equipped with strong manufacturing capabilities using microfluidics for scalable control over particle size, and our analytical capabilities ensure precise characterization of our LNPs.
LipExoGen is committed to accelerating the drug development journey from discovery to clinical trials. Our synthesis platform supports micro to liter scale production with rigorous quality control, from in vitro functional assays to sterile filtration. LipExoGen value collaboration, working closely with our clients to navigate project complexities and achieve milestones efficiently. Whether it's a low-risk pilot study or comprehensive data packages for grant applications, LipExoGen is your partner in driving the success of next-generation mRNA-based therapies.
Capabilities
Encapsulate a wide variety of cargo:
Messenger RNA (mRNA)
Small interfering RNA (siRNA)
Single guide RNA (sgRNA)
Micro RNA (miRNA)
Antisense oligonucleotide (ASO)
ODN CpG
DNA
Surface modify for specific targeting and other properties:
Monoclonal antibodies
scFV or Fab
Nanobodies
Proteins
Cytokines
Protein functional domains
Fusion proteins
Peptides (e.g. cRGD)
Aptamers
Glycosylation
Small molecule ligands (e.g. folate, etc.)
Reduction of non-specific uptake
Incorporate fluorescent dyes for in vivo imaging and cellular uptake assays
Strong manufacturing capabilities
Microfluidics for scalable control over particle size and PDI
Microliter to liter scales
Excellent analytical capabilities
Dynamic light scattering (DLS) analysis of particle size (Z-average) and polydispersity index (PDI)
Zeta potential, conductivity
Concentration
Encapsulation efficiency (EE)
HPLC, Ribogreen Assay
In vitro Functional Assays (transfection efficiency, cytotoxicity assays, etc.)
SDS-PAGE with Coomassie blue or Western blot for validation of antibody conjugation
Stability assays
Sterility
Sterile filtration with 0.22 micron PES
Dispensed in sterile glass vials free of endotoxin, pyrogens, DNAse and RNAse, stoppered and crimp-capped under sterile conditions
Additional Services
Low-risk and low cost pilot (feasibility) studies
Preliminary data packages for grant applications (academic only)
Site-specific antibody conjugation (linker restricted to Fc-region)
Figure 1. Specific uptake of LNPs in target cells. LNPs were synthesized containing 0.1% of the fluorescent dye DiI (red) and further modified to reduce non-specific cellular uptake. Last, LNPs were either surface modified by an anti-human CD20 antibody or left unmodified (naked) and applied to cells for 24 h before acquiring fluorescence microscopy images. Naked LNPs are not efficiently taken up by Raji cells because the LNPs were engineered to reduce non-specific cellular uptake (left). Conjugating an anti-CD20 antibody to the surface of the LNPs promotes their specific uptake in Raji cells, which are CD20+ (middle), but not in HEK293FT cells, which are CD20- (right). Our formulation experts can encapsulate the nucleic acid cargo of your choosing and surface modify the LNPs with any antibody you want to produce similar effects depending on the cells you wish to target.
Figure 2. Schematic components of mRNA LNPs. Lipid nanoparticles generally contain four major types of lipids. An ionizable lipid, such as MC3, constitutes the bulk of the lipid components and is responsible for the encapsulation of mRNA or other nucleic acid cargo. Under LNP synthesis conditions, the ionizable lipid is protonated and bears a positive charge which interacts with the negative charge of nucleic acids. At physiological pH, it is deprotonated and neutral, thus overcoming the drawback of cationic liposomes which are inherently toxic. Once endocytosed, the ionizable lipid becomes positively charged again and promotes membrane fusion allowing the cargo to be ejected into the cytosol. Helper lipids, such as DSPC and DOPE, play structural roles and are involved in the process of endosomal escape. Cholesterol is typically the second most abundant lipid component, which plays a structural role. A PEGylated lipid such as DMG-PEG2000 stabilizes the LNPs and allows small particle si
Figure 3. Schematic representation of the process for LNP synthesis. Nucleic acid cargo and lipids are first dissolved at an appropriate concentration in separate solutions. The controlled mixing of the aqueous and organic phases results in lipid nanoparticle self-assembly and encapsulation of the therapeutic molecule such as mRNA. An ionizable lipid bears a positive charge under specific pH values used for lipid nanoparticle synthesis, but is deprotonated at physiological pH making it neutral. During LNP synthesis, the charge interaction between ionizable lipid and the phosphates present in nucleic acids drives encapsulation of the nucleic acid. Following LNP synthesis, buffer exchange is carried out to adjust the ionic strength and pH of the bulk solution for physiological applications. Surface modification with monoclonal antibodies or other proteins, peptides, aptamers, or other functional molecules can be performed to fine-tune the LNP properties. Fluorescent dyes can be included
Figure 4. EGFP mRNA LNPs in action. In vitro transfection of HEK293FT cells with EGFP mRNA LNPs is shown by fluorescence microscopy. The size distribution on the left shows the average particle diameter determined by dynamic light scattering (DLS). Note: in this example the LNPs were not engineered to reduce non-specific cellular uptake – therefore, no antibody or targeting molecule is required.