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.
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.1
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.
Inquire About Our ServicesA: Polyplexes are complexes formed between polycations and anionic nucleic acids, such as mRNA. Creative Biolabs utilizes polyplexes for mRNA delivery by designing and optimizing these complexes to protect mRNA molecules from degradation, enhance cellular uptake, and ensure efficient release of the mRNA into the target cells.
A: Creative Biolabs offers comprehensive services for polyplex preparation for mRNA delivery, including the selection of polycations, optimization of polyplex formation conditions, characterization of polyplex properties, and testing for delivery efficiency. They tailor their services to develop effective polyplexes suitable for various therapeutic applications.
A: Creative Biolabs optimizes polyplexes for effective mRNA delivery by adjusting parameters such as polycation type and molecular weight, charge ratio, size, and surface properties. They conduct extensive in vitro and in vivo testing to ensure that the polyplexes provide high encapsulation efficiency, stability, and effective mRNA release within target cells.
A: Creative Biolabs ensures the safety and biocompatibility of their polyplex formulations through rigorous testing and optimization. They evaluate cytotoxicity, immunogenicity, and biodistribution in both in vitro and in vivo models to confirm that their polyplexes are safe and well-tolerated in biological systems.
A: Creative Biolabs offers a range of customization options for clients, including custom polycation synthesis, formulation adjustments based on specific mRNA sequences, incorporation of targeting ligands, and scale-up production. Their team works closely with clients to develop tailor-made polyplex formulations that meet specific project requirements and therapeutic goals.
A: Clients can start a project with Creative Biolabs by reaching out to their customer service team to discuss their specific project needs and objectives. Creative Biolabs provides initial consultations, detailed project planning, and step-by-step guidance through the process of polyplex preparation and mRNA delivery optimization to achieve successful outcomes.
The experiment involved using polyplex formulations to deliver nucleic acids effectively. Polyplexes, which are complexes formed between cationic polymers and nucleic acids, were shown to aid in the delivery process by protecting the genetic material from degradation and enhancing cellular uptake. The results demonstrated that polyplex-delivered nucleic acids elicited significant biological responses. Specifically, the polyplex formulations proved to be efficient in delivering the nucleic acids to the target cells, leading to robust expression of the desired proteins and subsequent induction of immune responses. This highlights polyplexes' potential as a nonviral delivery system for nucleic acid-based therapeutics, showing promise for further development and application in gene therapy and vaccine delivery.
Fig.2 Bioluminescence after intranasally administering luciferase-expressing mRNA.2
Cat. No | Product Name | Promoter |
---|---|---|
CAT#: GTVCR-WQ001MR | IVTScrip™ pT7-mRNA-EGFP Vector | T7 |
CAT#: GTVCR-WQ002MR | IVTScrip™ pT7-VEE-mRNA-EGFP Vector | T7 |
CAT#: GTVCR-WQ003MR | IVTScrip™ pT7-VEE-mRNA-FLuc Vector | T7 |
CAT#: GTVCR-WQ87MR | IVTScrip™ pT7-VEE-mRNA-Anti-SELP, 42-89-glycoprotein Vector | T7 |
Cat. No | Product Name | Type |
---|---|---|
CAT#: GTTS-WQ001MR) | IVTScrip™ mRNA-EGFP (Cap 1, 30 nt-poly(A)) | Reporter Gene |
CAT#: GTTS-WK18036MR | IVTScrip™ mRNA-Human AIMP2, (Cap 1, Pseudo-UTP, 120 nt-poly(A)) | Enzyme mRNA |
(CAT#: GTTS-WQ004MR) | IVTScrip™ mRNA-Fluc (Cap 1, 30 nt-poly(A)) | Reporter Gene |
(CAT#: GTTS-WQ009MR) | IVTScrip™ mRNA-β gal (Cap 1, 30 nt-poly(A)) | Reporter Gene |
References