MRNA therapeutics against cancer and infectious diseases

Abstract

In vitro transcribed mRNAs are an ideal biologically active agent to be used as therapeutics in treatment of various disorders and as vaccines against infectious diseases and for cancer therapy. An optimized delivery system which gives efficient transfection with mRNA and is stable and non-toxic to the cells and organism, is key to the success of mRNA application. In this study, we use DC-cholesterol and DOPE based liposomes to deliver mRNA in vitro and in vivo. These cationic liposomes formed by simple steps, successfully encapsulated mRNA and facilitated strong transfection following in vivo delivery. There was no toxicity observed in the cells or in the mice. There was prolonged production of EGFP and luciferase reporters, indicating that there is a long-lasting effect of this delivery. Finally, the immunogenicity of antigens delivered by this complex was investigated by subcutaneous delivery of mRNAs encoding Streptococcus aureus antigen AdsA and tumor model antigen OVA. Therapeutic efficiency of OVA mRNA-liposome complex can be clearly seen and it shows that these mRNAs provoked a strong T cell response after delivery. Furthermore, we found that the DC cholesterol-packed mRNA is suitable for local delivery. When the packed mRNA encoding EGFP is injected intra-tumor, strong localized expression was observed in tumor. In summary, DC-cholesterol-DOPE cationic liposomes are safe and efficient in the delivery of mRNA and can be applied in the development of mRNA-based therapies.