Hybrid mRNA Delivery System

Hybrid delivery systems have evolved as promising biomaterials for mRNA delivery, owing to their superior physicochemical properties, such as multi-functionality and flexibility. The systems consist of a combination of various types of materials, including lipids, peptides and polymers. Therefore, they integrate all the benefits of each individual component. For mRNA delivery, the development of hybrid delivery carriers comprised various kinds of materials is a growing trend. In general, the hybrid delivery carriers share a tunable core-shell structure. The shell structure not only confer carriers tunable properties on the surface, but also improves the carrier's stability as well as pharmacokinetics. Meanwhile, the core structure can also be modified to facilitate endosomal escape according to external stimulus. IVT mRNA can be effectively delivered by the way of condensation in the core structure or surface adsorption of the shell structure. In addition, a series of lipids, polymers and other materials have been investigated to formulate the hybrid delivery system, including common polymers (such as PLGA, polycaprolactone, polylactic acid), lipids (such as DOTAP, DSPE, and PEG), peptides (protamine and positively charge short peptides). At present, there are several common hybrid systems studied for mRNA delivery.

The hybrid delivery system for IVT mRNA delivery

  • Lipid-polymer hybrid systems

Lipid-polymer hybrid systems consist of cationic polymers and lipids, also called lipopolyplexes, are an emerging mRNA delivery system. The hybrid systems have been applied for mRNA delivery to against several cancers and show a great application prospect, including melanoma tumor, prostate cancer. Besides, a hybrid polymer-lipid nanoformulation had been successfully used for systemic delivery IVT mRNA to the lungs and showed both enhanced serum stability and increased in vitro potency.

The schematic illustrations of structure of lipid-polymer hybrid nanoparticles(LPNs).Fig1. The schematic illustrations of structure of lipid-polymer hybrid nanoparticles(LPNs).( Zhao, W., et al., 2018).

  • Lipid-peptide hybrid systems

Lipid-peptide hybrid systems have been commonly studied for mRNA delivery. For example, complexes formed by IVT mRNA, protamine and lipid are designed to treat lung carcinoma, showing significant results in both efficacy and toxicity in animal models.

  • Multi-component hybrid systems 

Hybrid delivery systems for mRNA delivery can be formulated with more than two components. The multi-component hybrid systems are various, such as PEG-PAsp (TEP)-cholesterol nanosystems, the delivery system formed with poly(glycoamidoamine) (PGAAs) brush, and hybrid cationic nanoemulsion (CNE) (a vaccination formulation).

Service offering in Creative Biogene

With the years of experience in the development of mRNA delivery system, we are deeply aware that single functional delivery systems can't meet the increasing needs of application. Therefore, the development of hybrid delivery carriers comprised of various materials is a trend, owing to multi-functionality and flexibility. Creative Biogene currently provides several hybrid delivery system development services for mRNA delivery, including lipid-polymer hybrid systems, lipid-peptide hybrid systems and other multi-component hybrid systems. We will adopt a series of biodegradable and biocompatible materials and select the optimal assembly routes. mRNA delivery efficiency of different hybrid delivery systems will be evaluated and a systematic orthogonal optimization will be further performed. The hybrid mRNA delivery systems are developed in accordance with the several structure/activity relationships, involving the number of amino groups, hydroxyl groups, and shorter alkyl tails for efficient delivery.

Compared with non-hybrid delivery systems, hybrid delivery carriers present more flexibility and delivery efficiency due to assembling several potential advantages of their components. However, the synthesis of hybrid delivery systems is complex and full of challenges. Based on experienced experts and state-of-the-art equipment and technology, Creative Biogene is confident in offering the most suitable hybrid mRNA systems for the specific project of customers from all over the world. Our service includes one-stop solution of hybrid delivery system development, and transfer as well as implementation of existing hybrid delivery system. Simply let us know about your research needs. We will propose the best strategy to best match your research objectives. Contact us right now!


  1. Guan, S., & Rosenecker, J. (2017). "Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems." Gene therapy, 24(3), 133-143.
  2. Siewert, C. D., et al. (2020). "Hybrid biopolymer and lipid nanoparticles with improved transfection efficacy for mRNA." Cells, 9(9), 2034.
  3. Zhao, W., et al. (2018). "Lipid polymer hybrid nanomaterials for mRNA delivery." Cellular and molecular bioengineering, 11(5), 397-406.
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