Novel Strategies of Adjuvant Development
Efforts to develop mRNA vaccines have been involving the supplement of additional adjuvant molecules, substances formulated as a component of vaccine to enhance and broaden the vaccine's effectiveness. Apart from the conventional adjuvants, mRNA vaccines can be designed to possess self-adjuvanticity because in vitro transcribed (IVT) mRNA has shown inherent immunogenicity. In addition, mRNA vaccines co-delivery with mRNA encoding costimulatory molecules also present a promising approach to further boost vaccines' immunogenicity.
Creative Biogene is a dedicated service provider in the field of mRNA-based drug R&D. We offer novel strategies to develop adjuvants for mRNA vaccines, including design and production of self-adjuvanticity mRNAs and additional mRNA encoding adjuvant molecules. With the help of Creative Biogene, our customers can obtain optimized mRNA vaccines for specific and directed immune responses.
Adjuvanticity of RNA
The immunostimulatory properties of RNA were first discovered through the observation that exogenous RNA extracted from viruses inducing interferon in vitro, and then further confirmed by the synthetic double-stranded RNA (dsRNA) in vivo induction of interferon. After IVT mRNA is transported to the host cell, it is detected and recognized by the cellular activated pattern recognition receptors (PRRs). PRRs contain Toll-like receptors (TLRs, in the endosome), RIG-I-like receptors (RLRs, in the cytoplasm) and Nod-like receptors (NLRs, in the cytoplasm). As RNA-sensing receptors, TLR7/8 and 3 can bind single-stranded RNA (ssRNA) and dsRNA in the endosomal compartment, respectively. Notably, for mRNA vaccines, the activation of TLR7 and potentially TLR3 play critical roles in priming immune responses. In addition, apart from TLR RNA-sensors, other pattern recognition receptors exist with important functionality for RNA adjuvant, such as the cytosolic helicase RIG-I, protein kinase R (PKR) as well as 2'-5'-oligoadenylate synthetase and so on. But their contribution to immunostimulation based on RNA adjuvants is still a matter of debate.
We are committed to designing mRNA incorporating immunostimulatory adjuvant functionality, a novel strategy of adjuvant better suited for mRNA vaccines. The technology relies on mRNA molecules treated with ssRNA or dsRNA, allows efficient antigen protein translation and immunostimulation with minimal adverse effects. Moreover, compared with the addition of conventional adjuvant in mRNA vaccines, the RNA formulation is universal, and can be introduced with mRNA by a wide range of mRNA delivery carriers.
Proteins are expressed after mRNA is administered in vitro and in vivo. The supplement of adjuvant molecules via mRNA, instead of adding additional adjuvants, appears as a more elegant and powerful approach. We provide services that design and produce mRNA encoding adjuvant molecules, involving costimulatory molecules, such as CD40L, CD70, GITR and so on. The combination of mRNA vaccines and additional mRNAs encoding adjuvant molecules represents a very promising approach, greatly promoting the development of novel and improved vaccines.
Benefits of our service
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Creative Biogene is passionate about strong customer orientation and high-quality service. We continuously challenge ourselves to remain one of the leading service providers in the field of mRNA-based drug R&D worldwide. If you are interested in our service, please contact us for more information!
- Schlake, T., et al. (2012). "Developing mRNA-vaccine technologies." RNA biology, 9(11), 1319-1330.
- Uchida, S., et al. (2018). "Designing immunostimulatory double stranded messenger RNA with maintained translational activity through hybridization with poly A sequences for effective vaccination." Biomaterials, 150, 162-170.