Advances in mRNA therapeutics for cancer immunotherapy: From modification to delivery

  • Han, Geonhee
  • Noh, Dahye
  • Lee, Hokyung
  • Lee, Sangmin
  • Kim, Sehoon
  • Yoon, Hong Yeol
  • Lee, Soo Hyeon

  • aKU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea

    bMedicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea

    cDivision of Bio-Medical Science &Technology, KIST School, University of Science and Technology, Hwarang-ro14-gil 5, Seongbuk-gu, Seoul, Republic of Korea 02792

    dDepartment of Fundamental Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 02447, Republic of Korea

    eChemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea

    fMolecular Surgery Laboratory, Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, CA 94304, USA

*Corresponding authors at: Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea (H.Y.Y.) and Molecular Surgery Laboratory, Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, CA 94304, USA (S.H.Lee.).

E-mail address:[email protected]; [email protected].

Article history: Received March 31, 2023; Received June 13, 2023; Accepted June 21, 2023.

ARTICLE INFO

Advanced Drug Delivery Reviews 199:p 114973, August 2023. | DOI: 10.1016/j.addr.2023.114973

Highlights

  • Biological and pharmacological limitations constrain the utility of mRNA therapeutics.

  • Chemical modification of mRNA increases biological stability and reduces side effects.

  • Non-viral delivery systems increase pharmacological potential of mRNA.

  • mRNA is a potent therapeutic agent for cancer immunotherapy.

Graphical abstract

RNA vaccines have demonstrated their ability to solve the issues posed by the COVID-19 pandemic. This success has led to the renaissance of research into mRNA and their nanoformulations as potential therapeutic modalities for various diseases. The potential of mRNA as a template for synthesizing proteins and protein fragments for cancer immunotherapy is now being explored. Despite the promise, the use of mRNA in cancer immunotherapy is limited by challenges, such as low stability against extracellular RNases, poor delivery efficiency to the target organs and cells, short circulatory half-life, variable expression levels and duration. This review highlights recent advances in chemical modification and advanced delivery systems that are helping to address these challenges and unlock the biological and pharmacological potential of mRNA therapeutics in cancer immunotherapy. The review concludes by discussing future perspectives for mRNA-based cancer immunotherapy, which holds great promise as a next-generation therapeutic modality.

Copyright © 2023Elsevier, Inc.