blog

The history of RNA vaccines

Written by Alejandra Carreira | Apr 2025

RNA vaccines have revolutionized the field of immunization. From basic discovery to global deployment, mRNA vaccine technology has emerged as a powerful platform for combating infectious diseases, cancer, and more. In honor of World Immunization Week, this comprehensive guide explores the history of RNA vaccines, their scientific breakthroughs, and where the field is heading next.

Questions answered in this post:

    • How were mRNA vaccines developed? The first mRNA experiment was published in 1978. Since then, decades of research led to the approval of COVID-19 mRNA vaccines in 2020.

    • Why are LNPs used for mRNA vaccines? Lipid nanoparticles protect mRNA from degradation and improve delivery to cells. They are the most effective delivery system available today.

    • What are the benefits of RNA vaccines? Fast to develop, adaptable, and capable of targeting multiple diseases, RNA vaccines represent a flexible platform for future healthcare needs.

Timeline of the main milestones in the history of RNA vaccines

 

What are the benefits of RNA vaccines compared to DNA or antigen Delivery?

  1. No Requirement for Nuclear Entry: Unlike DNA vaccines, mRNA vaccines do not need to enter the cell nucleus to be effective. This eliminates the risk of genomic integration and allows for faster protein expression.

  2. Faster Development and Manufacturing: mRNA vaccines do not require extensive protein purification or the use of adjuvants, simplifying the development and manufacturing process. RNA is also highly adaptable, allowing rapid redesign to address emerging pathogens.

  3. Induction of Robust Immune Responses: RNA vaccines can induce both humoral and cellular immune responses, contributing to robust and durable protection.

 

Key developments in the RNA field

1961: Discovery of mRNA

Jacob and Monod's foundational work identified messenger RNA as the intermediary between DNA and protein synthesis, introducing a concept vital for gene expression technologies and laying the groundwork for RNA-based therapeutics.

1978: First Functional mRNA Delivery

Dimitriadis demonstrated that liposome-encapsulated mRNA could be delivered into mammalian cells, leading to successful translation of encoded proteins within the cell.

1984: Lab Synthesis of Biologically Active mRNA

Researchers synthesized biologically active mRNA in vitro and showed it could direct protein production in frog eggs, setting the stage for RNA-based experiments.

1989: Lipid-Mediated mRNA Delivery into Human Cells

Cationic liposomes were used to deliver mRNA into human cells and frog embryos, demonstrating a method to effectively deliver RNA across membranes.

1990: In Vivo Translation of IVT mRNA

Researchers injected in vitro transcribed mRNA into live mouse muscle, resulting in protein expression and proving that mRNA could be a viable in vivo therapeutic.

1993: Functional Immune Response from mRNA in Animals

Studies showed that liposome-delivered mRNA could trigger immune responses in animal models. 

1999: Lipid Nanoparticles for Nucleic Acid Delivery

Pieter R. Cullis and colleagues developed ionizable lipid-based vehicles —today known as lipid nanoparticles (LNPs) — that enhanced nucleic acid encapsulation, endosomal escape, and delivery efficiency, revolutionizing mRNA therapeutics.

2005: Pseudouridine and Immune Evasion

Synthesizing mRNA incorporating pseudouridine prevents innate immune activation, significantly improving RNA stability, translation, and therapeutic safety.

 

Clinical Trials of mRNA Vaccines

2010s: Early Human Trials

Cytomegalovirus (CMV), and influenza and rabies mRNA vaccines entered phase 1 clinical trial in humans, showing promising safety and immunogenicity.

2020: COVID-19 as a Tipping Point

The success of the first mRNA-based vaccines (BNT162b2 and mRNA-1273) marked a clinical breakthrough. 

 

The Future of RNA Vaccines

RNA technology is expanding rapidly. Ongoing clinical programs are exploring mRNA vaccines for tuberculosis, malaria and HIV. Neoantigen-based cancer vaccines and personalized therapies are also under active investigation. Innovations like self-amplifying RNA (saRNA), circular RNA (circRNA), and thermostable mRNA formulations promise broader global access and improved durability.

 

Why CATUG is Your RNA Innovation Partner

Industry-leading RNA-LNP expertise
We've manufactured 600+ DNA and RNA sequences and 100+ LNP formulations.
 
Custom RNA and LNP synthesis
Custom RNA synthesis (mRNA, saRNA, circRNA, tRNA and siRNA) paired with precise LNP formulation.
 
From early-stage to GMP-grade manufacturing
Seamless scale-up from research or preclinical studies to commercial production.
 
Regulatory compliance
Facilities compliant with FDA, EMA, and ICH guidelines.

 

Whether you're developing a RNA-based vaccine, a therapeutic, or a research tool, we can help you move from concept to clinic with confidence and speed.

Explore our RNA and LNP services and partner with us to bring your RNA product to life.

 

 

About CATUG

CATUG is a CRDMO for RNA therapeutics. We help academia and biotech companies to develop their projects efficiently, offering research support, CMC services, and GMP manufacturing. We work with labs of all sizes and stages, from research & discovery and clinical trials to product manufacturing for commercial use.