In the past decades, mRNA has been widely used in the biomedical field. However, the efficient expression of mRNA is still one of the key challenges in its wide clinical application. Although some of these challenges have been partially solved by chemical modification, intracellular delivery of mRNA remains a major obstacle. Polymer-based vectors are a delivery technology that can ensure the stability of mRNA under physiological conditions, and can guarantee the clinical translation of mRNA-based therapies.
Polymers, a class of natural or synthetic substances composed of very large molecules, are multiples of simpler chemical units. Polymeric nanoparticles (PNPs) are the most common materials studied as nanocarriers for drugs and gene delivery. Generally, polymers designed and studied for gene delivery include: polyethyleneimine (PEI) and its derivatives; polymethacrylate; carbohydrate-based polymers, usually β-cyclodextrin, chitosan, dextran and poly(glycosylamine) as their carbohydrate functional groups; dendrimer-based vectors, such as polyamidoamine dendrimers (PAMAM) and poly(propylene diamine) (PPI) dendrimers, etc.
The preparation of PNPs includes two methods: a top-down strategy (grinding prefabricated polymers to appropriately sized particles) or a bottom-up strategy (requiring the use of conventional multi-reaction direct polymerization monomers).
Fig.1 Summary of top-down and bottom-up techniques for generating PNPs.1
As an important non-viral vector, the polymer gene delivery system has attracted more and more attention, and has begun to show more and more prospects.
Common organic compounds, such as cellulose or lignin, are the most abundant biopolymers on earth, defining the possibility of multiple structures and conformations.
Most of the new technology of polymer gene transfer aims at two main aspects at the same time, namely: (1) the best transfer of gene in the target cell and (2) the minimum retention of transfer vector in vivo to eliminate toxic effect. Natural or synthetic biodegradable polymers with various functional designs can play this role well.
Polymers can be dissolved in a wide range of common solvents, which makes functionalization and other chemical modifications quick and easy. In addition, after a long time of exploration and summary, polymer synthesis technology has been mature and suitable for large-scale industrial production.
In order to provide a powerful mRNA delivery system, we have now mastered the construction and synthesis technology of two different polymer complexes, micelleplex- and polyplex-type.
Because of the positive charge, the polycation can spontaneously combine with the negatively charged nucleic acid phosphate skeleton to form a "polyplex", to facilitate gene transfer. The polyplex formed between cationic polymer and genetic material is based on electrostatic interaction. The molecular weight, hydrophilicity, surface charge and structure of the cationic polymer determine the efficiency of the carrier.
Fig.2 Polyplex formation.
According to the composition and structure of block copolymers, micelleplexes with different morphology and stability can be prepared. They have many important properties, such as self-assembly, micellization, biocompatibility, thermodynamic stability, large exclusion volume, effective condensation and protection of RNA, low toxicity, and the ability to combine with biofilm, which contribute to the successful application of RNA therapy technology in clinical (enhance cell interaction and gene transfection) and improve intracellular transport through endoplasmic body escape mechanism.
Fig.3 Schematic illustration of the micelleplexes.2
Creative Biolabs spares no effort to provide customized polymer-based vector synthesis and production for customers from all over the world. Compared with traditional PNPs, our products have a higher gene transfection rate, which can achieve sustained and controllable release of therapeutic genes and cell targeting. If you have any need, please contact us.
Inquire About Our ServicesA: Polymer-based vectors are delivery systems composed of synthetic or natural polymers designed to encapsulate and transport therapeutic molecules to target cells or tissues. These vectors are used for drug delivery because they can protect the therapeutic cargo, enhance stability, control release profiles, and potentially improve targeting and bioavailability.
A: Creative Biolabs offers a range of polymer-based vector services, including polymer design and synthesis, formulation and optimization of polymer-based vectors, encapsulation efficiency analysis, stability and release profile assessment, biocompatibility and toxicity studies, and in vitro and in vivo delivery efficacy testing.
A: Polyplex-based delivery systems involve the use of positively charged polycations that combine with negatively charged nucleic acid phosphate skeletons through electrostatic interactions. The efficiency of these carriers is determined by factors such as molecular weight, hydrophilicity, surface charge, and structure of the cationic polymer.
A: Creative Biolabs offers end-to-end support in the development process of polymer-based vectors, including initial consultation and project planning, polymer synthesis and vector formulation, optimization of delivery systems, analytical characterization, preclinical testing, and regulatory support. Our team of experts collaborates closely with clients to ensure the successful development and implementation of polymer-based vector systems for their specific applications.
A: Polymer-based vectors offer several advantages for gene and drug delivery, including high biocompatibility, tunable degradation rates, capacity for high payload encapsulation, and flexibility in modifying surface properties for targeted delivery. These vectors can also provide controlled and sustained release of therapeutic agents, which can enhance treatment efficacy and reduce side effects.
This study investigates polymer-based nanoparticles for inhalable mRNA delivery to the lungs, aimed at treating pulmonary diseases. The researchers developed a polymer-based vector called PACE (Poly(amine-co-ester), which addresses issues of poor transfection efficiency and vehicle-induced pathology. PACE nanoparticles demonstrated effective delivery and expression of therapeutic mRNA in lung tissue without causing significant inflammation or toxicity. This platform shows promise for non-invasive, targeted mRNA therapeutics for lung diseases, indicating potential for clinical applications in vaccination and protein replacement therapies.
Fig.4 Characterization of PACE-mRNA polyplexes and in vitro activity.3
| 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
