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The metabolic instability of mRNA currently limits its utility in gene therapy. Compared with plasmid DNA, mRNA is more easily digested by RNase after systemic administration. Therefore, mRNA-based therapy combined with effective delivery systems, such as polyplex, is a promising method for the treatment of refractory diseases related to excessive apoptosis.

Introduction of Polyplex

Cationic polymer/therapeutic gene complexes (cationic polyplexes) can improve the cellular uptake of nucleic acid therapy drugs by interacting with negatively charged cell surface. The advantages of using cationic polyplexes include the protection of therapeutic genes from the influence of serum nucleases. The complexation of anionic mRNA molecules and cationic polymers occurs spontaneously through electrostatic interactions, forming polyplexes with multi-chains. They usually show higher stability than lipid complexes. It is also easy to modify polymers such as molecular weight, geometry (linear or branched) and ligand linkage.

In general, the resulting polyplexes are mostly small particles with particle size less than 200 nm, and the zeta-potential is +20 ~ +30 mV. Even at a low N/P ratio, stable polyplexes can be formed. These polyplexes have a wide range of characteristics, so they can show differences between different nucleic acid polymers, for example in terms of polyplex stability and anti-heparin effects.

Fig. 1 Formation of polyplexes with mRNA and uptake of the polyplex into cells. (Debus, et al., 2010)Fig. 1 Formation of polyplexes with mRNA and uptake of the polyplex into cells.1

Preparation of Polyplex for mRNA Delivery at Creative Biolabs

As a new therapeutic method, mRNA pharmaceuticals are widely used in cancer vaccine, tumor therapy and protein replacement. The target of receptor-mediated cell uptake and post-translational induction of gene transfection needs to be formulated to deliver mRNA to the target sites.

Several polyplexes for mRNA delivery have been successfully prepared by Creative Biolabs. These include polyethyleneimine (PEI) polyplex nanoparticle, which is one of the most commonly used cationic polymers in gene and oligonucleotide transfer; CP/mRNA polyplexes, which are synthesized by β-cyclodextrin (molecular weight 1135 Da) and branched PEI2k or PEI600; poly(2-dimethylaminoethyl methacrylate) (PDMAEMA), etc. These polymers have been tested in vitro and in vivo, and have been proven to be mRNA delivery vectors, forming multi-chain nanoparticles together with mRNA, promoting the whole-body mRNA delivery and subsequent in vivo translation.


Nucleic acid therapeutics with many advantages are expected to rapidly expand the market. Creative Biolabs is a biotechnology company dedicated to the discovery of nucleic acid therapeutics based on novel drug delivery platforms in the field of unmet medical needs. We spare no effort to provide customized polyplex synthesis and production for customers from all over the world. If you are interested in our services, please feel free to contact us.


  1. Debus, Heiko, et al. "Delivery of messenger RNA using poly (ethylene imine)-poly (ethylene glycol)-copolymer blends for polyplex formation: Biophysical characterization and in vitro transfection properties." Journal of Controlled Release 148.3 (2010): 334-343.
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