Poster abstracts

Poster number 17 submitted by Peixuan Guo

Development of cancer mRNA vaccine and immune therapy agent by applying RNA nanotechnology, chemical modification, and structure conversion of mRNA

Margaret Bohmer (Center for RNA Nanobiotechnology and Nanomedicine; RNA Biological Center; College of Pharmacy; College of Medicine; Comprehensive Cancer Center; OSU, Columbus, Ohio), Daniel Binzel (Center for RNA Nanobiotechnology and Nanomedicine; RNA Biological Center; College of Pharmacy; College of Medicine; Comprehensive Cancer Center; OSU, Columbus, Ohio), Kai Jin (Center for RNA Nanobiotechnology and Nanomedicine; RNA Biological Center; College of Pharmacy; College of Medicine; Comprehensive Cancer Center; OSU, Columbus, Ohio), Peixuan Guo (Center for RNA Nanobiotechnology and Nanomedicine; RNA Biological Center; College of Pharmacy; College of Medicine; Comprehensive Cancer Center; OSU, Columbus, Ohio)

Abstract:
The emerging phenomena have signaled that RNA therapeutics will be the third milestone in pharmaceutical drug development. The dynamic nature of RNA results in its motile and deformable behavior. These properties of RNA nanoparticles have resulted in 1) fast and efficient tumor accumulation via both spontaneous and active targeting, and 2) fast renal excretion for those non-tumor-accumulated nanoparticles due to RNA’s negative charge and the dynamic property, thus undetectable toxicity. The biodistribution of RNA nanoparticles was further improved by the incorporation of ligands for cancer targeting. Cancer mRNA vaccination and immune therapy have faced one challenge: mRNA is hundreds of nm. The delivery of the lengthy mRNA to specific cancer cells is difficult. Someone tried to use the extracellular vesicles (EV) and exosomes (EX) to load the mRNA, but the loading of the lengthy mRNA to EV/EX is difficult, especially for EX, which is about 50-120 nm, smaller than the mRNA. In our study, we used RNA Nanotechnology to compact the mRNA into small RNA Nanoparticles for EV/EX loading. RNA nanoparticles possess the properties of self-assembly, programmable, and multi-valency, making them a great material for application in vaccine development and cancer immunotherapy. We will present how to apply RNA nanotechnology for mRNA vaccine delivery, ligand-conjugation, T cell bi-specific targeting, T cell activation, checkpoint binding, dendritic cell delivery, and RNA vaccine adjuvant design. Using a bispecific RNA-T-cell engager with the ligand that binds to 4-1BB, it was found that T cells were activated, developed into a special type of T-cell. Cancer growth was inhibited. The RNA nanoparticle carrying three 4-1BB showed the strongest T-cell activation and cancer inhibition effect. Extracellular vesicles or exosomes have a great potential for loading and delivery of mRNA for cancer vaccination and immune therapy.

References:
1.Binzel DW, Guo P. Nanomedicine, 2025, 1–3.
2.Bohmer M, Binzel DW, Zhang W, Guo P. RNA, 2025 Apr 1:rna.080383.125.
3.Shu D, Bhullar A, Liang C, Zhang L, Guo P. Nucleic Acids Research, 2025, 53, 6, gkaf242
4.Bhullar A, Jin K, Shi H, Jones A, Hironaka D, Xiong G, Xu R, Guo P, Binzel D, Shu D. Mol Ther. 2024, 32, 12, 4467-4481
5.Binzel D, Li X, Burns N, Khan E, Lee W, Chen L, Ellipilli S, Miles W, Ho Y, Guo P. Chem. Rev., 2021, 121, 13, 7398-7467
6.Shu D, Zhang L, Bai X, Yu J, Guo P. Molecular Therapy Nucleic Acids. 2021 Mar. 24, 426-435

Keywords: RNA therapeutics , mRNA vaccine , RNA Nanotechnology