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LPR Technology

mRNA therapeutics have aroused great attention in several clinical settings. To meet the challenging requirements, Creative Biolabs has built a team of experienced scientists with facilities and processes designed specifically to provide the best strategy and protocols in the field of mRNA study. With our extensive experience and advanced LPR technology platform, we have won a good reputation among our worldwide customers for accomplishing numerous challenging projects in this field.

Introduction to mRNA Delivery

Dendritic cells (DCs), a class of antigen-presentation cells (APCs), are important to regulate the immune responses against bacterial or viral infections and other diseases. In general, genetically engineered tumor-antigen specific DCs have been commonly used in the development of cancer vaccines and cancer immunotherapy. Among them, in vitro transcribed (IVT) mRNA transfected DCs have been regarded as a perfect delivery system for transferring tumor antigens to target sites. Furthermore, pilot studies have demonstrated that the level of antigens expressed by mRNA-transfected DCs depends on the property of mRNA transcription and the efficacy of transfection reagents.

Normally, mature mRNA contains a 5' and a 3' untranslated region (UTR), an open reading frame (ORF), a cap structure at 5' terminus, and a Poly(A) tail residues at 3' terminus. Cationic liposomes and peptides are commonly engineered with mRNA to induce enough immune responses against diseases. Of note, lipopolyplexes (LPR), a complex of liposomes, polymer, and mRNA, have shown promise in delivering different kinds of mRNA encoding antigens in vivo. For example, recent researchers have revealed that MART-1 mRNA LPR is a powerful tool for developing mRNA-based vaccines for melanoma therapy.

Fig. 1 Representative scheme of the structure and preparation of different nonviral vectors for IVT-mRNA delivery. (Guan & J., 2017)

Fig. 1 Representative scheme of the structure and preparation of different nonviral vectors for IVT-mRNA delivery.1

Our LPR Technology Platform

Currently, Creative Biolabs has established a comprehensive LPR technology platform, from fully understanding and identifying your requirement to commercial-stage mRNA products manufacturing. In our histidylated LPR technology, the mRNA encoding a wide variety of tumor antigens is modified by specific histidylated liposomes and polymers. Firstly, mRNA is engineered with PEG-HpK histidine, and then liposomes are added into the mRNA complex to boost the mRNA delivery more safely and effectively. Moreover, we have also generated a mannosylated LPR technology for enhancing the transfection efficiency of mRNA-transfected DCs in vivo and the antitumor efficacy both in preclinical and clinical trials. Mannosylated liposomes are generated by inserting mannose aldehyde lipids into liposomes to favor DC anchoring. In a recent project, mRNA mannosylated LPR has shown a greater inhibition of tumor growth in melanoma models. As a result, with years of experience, we are capable of optimizing the development workflow to improve mRNA delivery, reduce overall cost, and shorten mRNA therapeutics development time.

What Can We Do?

  • PEGylated Histidylated Polylysine Synthesis
  • Lipids Synthesis
  • DNA Linearization and mRNA Synthesis
  • DNA and mRNA Analysis Studies
  • Preparation of Mannosylated Liposomes
  • Lipopolyplex Size and Potential Measurements
  • mRNA Transfection Assays

Based on our advanced LPR technology, Creative Biolabs is willing to provide the best-customized mRNA services for our clients. Please do not hesitate to contact us for more information.

Reference

  1. Guan, S., and J. Rosenecker. "Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems." Gene therapy 24.3 (2017): 133-143.
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