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Acta biomaterialia
09 01, 2021;131 1-15.

Synthetic modified messenger RNA for therapeutic applications.

Minsong Gao, Qingyi Zhang, Xin-Hua Feng, Jianzhao Liu
Author Information
  1. Minsong Gao: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Zheda Road 38, Hangzhou 310027, China.
  2. Qingyi Zhang: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Zheda Road 38, Hangzhou 310027, China.
  3. Xin-Hua Feng: Life Sciences Institute, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, China.
  4. Jianzhao Liu: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Zheda Road 38, Hangzhou 310027, China.; Life Sciences Institute, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, China.. Electronic address: liujz@zju.edu.cn.
PMID: 34133982 DOI: 10.1016/j.actbio.2021.06.020

Abstract

Synthetic modified messenger RNA (mRNA) has manifested great potentials for therapeutic applications such as vaccines and gene therapies, with the recent mRNA vaccines for global pandemic COVID-19 (corona virus disease 2019) attracting the tremendous attention. The chemical modifications and delivery vehicles of synthetic mRNAs are the two key factors for their in vivo therapeutic applications. Chemical modifications like nucleoside methylation endow the synthetic mRNAs with high stability and reduced stimulation of innate immunity. The development of scalable production of synthetic mRNA and efficient mRNA formulation and delivery strategies in recent years have remarkably advanced the field. It is worth noticing that we had limited knowledge on the roles of mRNA modifications in the past. However, the last decade has witnessed not only new discoveries of several naturally occurring mRNA modifications but also substantial advances in understanding their roles on regulating gene expression. It is highly necessary to reconsider the therapeutic system made by synthetic modified mRNAs and delivery vectors. In this review, we will mainly discuss the roles of various chemical modifications on synthetic mRNAs, briefly summarize the progresses of mRNA delivery strategies, and highlight some latest mRNA therapeutics applications including infectious disease vaccines, cancer immunotherapy, mRNA-based genetic reprogramming and protein replacement, mRNA-based gene editing. STATEMENT OF SIGNIFICANCE: The development of synthetic mRNA drug holds great promise but lies behind small molecule and protein drugs largely due to the challenging issues regarding its stability, immunogenicity and potency. In the last 15 years, these issues have beensubstantially addressed by synthesizing chemically modified mRNA and developing powerful delivery systems; the mRNA therapeutics has entered an exciting new era begun with the approved mRNA vaccines for the COVID-19 infection disease. Here, we provide recent progresses in understanding the biological roles of various RNA chemical modifications, in developing mRNA delivery systems, and in advancing the emerging mRNA-based therapeutic applications, with the purpose to inspire the community to spawn new ideas for curing diseases.

Keywords

RNA base modifications Synthetic modified mRNA Therapeutic mRNA mRNA delivery mRNA vaccines

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MeSH Term

COVID-19
COVID-19 Vaccines
Humans
Immunotherapy
RNA, Messenger
SARS-CoV-2

Chemicals

COVID-19 Vaccines
RNA, Messenger
Journal Article Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 47

Word Cloud

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