# Beginning of a new era of synthetic messenger RNA therapeutics: Comprehensive insights on mRNA drug design, development and applications

**Authors:** Saumya Nishanga Heendeniya, Suxiang Chen, Saadia Bhatti, Qurat Ul Ain Zahra, Kamal Rahimizadeh, Bal Hari Poudel, Stephen D. Wilton, Rakesh N. Veedu

PMC · DOI: 10.3389/ebm.2025.10784 · 2025-12-12

## TL;DR

This review explores how mRNA therapeutics, like those used in the SARS-CoV-2 vaccine, are being developed for a range of medical applications due to their safety and versatility.

## Contribution

The paper provides a comprehensive overview of mRNA drug design, development, and therapeutic applications, highlighting recent advancements and strategies.

## Key findings

- mRNA therapeutics offer safety due to their non-integration with the host genome.
- Biomodifications and chemical advancements have improved mRNA stability and reduced immunogenicity.
- mRNA strategies include protein replacement, immune modulation, and cellular modulation for diverse therapeutic uses.

## Abstract

Messenger RNA (mRNA) therapeutics have significantly transformed contemporary medicine, particularly through their role as the active component in the SARS-CoV-2 vaccine. This remarkable achievement is the culmination of extensive research conducted over many years by scientists. The widespread administration of the COVID-19 vaccine has further accelerated research into the precise therapeutic potential of mRNA technologies. Since mRNA doesn’t integrate with the host genome, the safety and versatility of mRNA-based therapeutics make them an iconic candidate in targeted therapies. Due to a surge in innovation efforts, biomodification of the molecular signatures of mRNAs like the 5′cap, untranslated regions (UTRs), and the poly(A) tail are being developed to increase translation efficacy. Recent advancements in chemical modifications, codon optimization techniques, and targeted delivery methods have significantly enhanced the stability of synthetic mRNAs while concurrently reducing their immunogenicity. Various mRNA manufacturing and synthesizing methods are investigated in this review, focusing on their scalability and limitations. mRNA therapeutic strategies can be divided into protein replacement, immune modulation, and cellular modulation. This review explores mRNA’s molecular landscape and comprehensive utility, including applications in both clinical trials and commercial sectors.

## Linked entities

- **Diseases:** SARS-CoV-2 (MONDO:0100096)

## Full-text entities

- **Diseases:** COVID-19 (MESH:D000086382)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12824530/full.md

---
Source: https://tomesphere.com/paper/PMC12824530