Peptide-Based mRNA Delivery System

For treatment and prevention of pathological diseases, designed IVT mRNAs are delivered into target cells, thus achieving the specific modulation of specific gene expression. However, mRNAs themselves, with large sizes, negative charges and other inherent hinders, can't be applied directly due to their low stability, poor intracellular uptake. With the development of bioscience and nanotechnology, a broad range of materials have been selected and developed to form mRNA delivery systems. Peptides consist of one or various amino acids monomers linked of peptide bonds, showing good biocompatibility, biodegradability, and bioactivity. Peptide-based and polypeptide-based systems for mRNA delivery are gaining momentum owing to their superior physicochemical properties. As a leading custom service provider in mRNA-based drug research and development (R&D), Creative Biogene focuses on mRNA delivery system development. With years of experience in mRNA delivery system development, we spare no effort to provide custom polypeptide-based mRNA carrier design, synthesis and production service for customers from all over the world. 

Introduction of peptide-based delivery system for IVT mRNA delivery

Recently, peptide-based and polypeptide-based delivery systems have attracted more and more attention for mRNA delivery, thanks to their unique advantages, including biocompatibility, biodegradability as well as bioactivity. Peptides are biologically occurring chains containing amino acids disposed of in block or random sequences. They take part in a series of normal metabolism, such as signal transduction, antigen-antibody reactions and among others. Therefore, comprised of biodegradable naturally occurring monomeric units, these materials hold great potential and can be prospectively applied in mRNA delivery in vivo.

Polypeptide-based system. Fig1. Polypeptide-based system. (Gómez-Aguado, I.,, 2020)

  • Protamine

Protamine is an arginine-rich small protein obtained from mature sperm of fish. As a common material used for mRNA transfection, the use of this small peptide as an enhancer of RNA uptake can go back towards 50 years ago and even earlier. The presence of arginines is responsible for the strong affinity to mRNA via electrostatic interactions. Protamine not only protects IVT mRNA from ribonuclease degradation, but also can be applied as an adjuvant for vaccination. Protamine-based formulations for IVT mRNA delivery are the second most used chemical systems. However, it is gradually replaced by lipide-based delivery system, which presents a better performance on mRNA protection and delivery efficiency.

  • Cell-penetrating peptides (CPPs)

The mechanisms by which CPPs promote cellular internalization need to be further studied. With a strong transmembrane transport capacity with no tissue or cell type specificity, CPPs and CPP RALA (A cationic CPP containing the arginine-rich amphipathic RALA motif) have been used for IVT mRNA delivery. CPP RALA has been pointed to outperform the cationic lipid DOTAP and the fusogenic lipid DOPE.

  • Artificial peptides

In addition, virus-like particles (VLPs) comprised of artificial viral coat proteins have been used to assemble and protect mRNA.

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, we are committed to developing safe and effective multifunctional systems for mRNA delivery, including multifunctional peptide-based and polypeptide-based delivery mRNA system. For the formulation of peptide-based and polypeptide-based mRNA delivery system, the peptides are mainly generated by genetic engineering according to the canonical genetic codes. We not only focus on basic biological properties of peptides, such as biodegradability and safety, but also on many other biological activities, including the spatial structure and modifications. Simply let us know about your research needs. We will propose the best strategy to best match your research objectives. Contact us right now!

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Polypeptide-based system.


  1. Gómez-Aguado, I., (2020). "Nanomedicines to deliver mRNA: state of the art and future perspectives." Nanomaterials, 10(2), 364.
For research use only. Not intended for any clinical use.
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