Lipid-Based mRNA Delivery System

An efficient IVT mRNA delivery vector or method is required to deliver synthetic mRNA into the cytoplasm of the target cells and efficiently release it to produce the desired protein. With years of efforts continuously developing new technologies, Creative Biogene is committed to meeting the growing demand for new mRNA delivery agents. We are now offering global customers lipid-based delivery system service, from lipid design to further optimization and testing. Based on state-of-the-art technologies and strict operation standards, we can offer a series of lipid-based vesicles, including lipid nanoparticles (LNPs), liposomes, and lipid emulsions. We guarantee to offer our customers with the best collaborative experience and affordable high-quality products. Importantly, our systematic protocol is flexible, and can be adjusted accordingly to be delivered to particular target cell types and tissues.

The composition of lipid-based delivery system

The lipid-based delivery system is the most widely used non-viral carrier for IVT mRNA delivery. This delivery system is mainly comprised of cationic lipids, which can interact with the mRNA to form lipoplexes through electrostatic interactions. Although the rationales of lipid design for mRNA delivery need to be further investigated, several aspects have been identified to play important roles in delivery safety and efficiency. These aspects include the component ratio with selected phospholipid, lipids biodegradability as well as lipid saturation. 

At present, a series of lipids and lipidoids (lipid- like delivery molecules) have been investigated and designed for IVT mRNA delivery, which are mainly inspired by siRNA and plasmid DNA delivery. Among them, cationic lipids were previously utilized to complex IVT mRNA, including N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA), 1,2-dioleoyloxy-3-trimethylammonium propane chloride (DOTAP), and 1,2-dioleoyl-sn- glycero- 3-phosphoethanolamine (DOPE). DOTMA was the first synthetic cationic lipid for mRNA delivery. And DOTAP is derived from DOTMA. However, it shows greater efficacy as well as more economical to synthesize. Given its superior advantages, DOTAP has been used alone or in combination with zwitterionic lipid DOPE for mRNA delivery. Moreover, ionizable lipids are emerging as an alternative to the above conventional cationic lipids due to the same transfection capacity with lower toxicity. The members of ionizable lipids include 1,2-dioleoyl-3-dimethylammonium propane (DODAP) and 1,2-dioleyloxy-N,N-dimethyl-3-aminopropane (DODMA). Nowadays, delivery vehicles composed of ionizable cationic lipids are one of the leading delivery systems for IVT mRNA.

Fig1. Lipid-based system. (Gómez-Aguado, I., et.al., 2020)

Service offering in Creative Biogene

The physicochemical and structural characteristics of lipoplex will depend on the lipid composition, the ratio of mRNA to the total amount of (cationic/ ionizable) lipids, and the lipid synthesis. Based on deep and broad expertise in the targeted delivery of mRNA, we use combinatorial methods to identify novel compounds and optimize formulations for mRNA delivery vectors. We have put great efforts into modifying and optimizing candidate lipoplex based on optimized formulation parameters, to facilitate the endosome-to-cytosol transition of mRNA carriers.

The specific service includes,

• Extensive screening of potential candidates for the optimal lipid

- Synthesis of novel lipids according to target cells or tissues

- Formulation and complexation

• Testing and optimization

- Determination of a series of optimized formulation parameters

- in vitro and in vivo testing

- Repeated optimization

Service workflow

If you are interested in our services, please contact us for more information. We are glad to cooperate with you!