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mRNA technology: navigating preclinical research for rare diseases

By Philip Cruz, Country Medical Director at Moderna UK

The Persistent Challenge of Rare Diseases

Rare Disease Day serves as a poignant reminder of the critical need to focus on less common ailments that significantly impact patients, their families, healthcare providers, and researchers dedicated to uncovering viable treatments.

Of the over 7,000 identified rare diseases affecting more than 300 million individuals worldwide, a staggering 95% lack an approved treatment1,2. These conditions often trace back to genetic mutations, manifesting as inherited disorders from birth.

The Potential of mRNA Technology

In the realm of genetic disorders, messenger RNA (mRNA) technology presents a novel investigative approach. It employs mRNA to potentially guide the body in producing specific proteins that are missing or dysfunctional in rare diseases, with the body naturally disposing of the mRNA once its function is completed3,4. While Moderna is recognised for its mRNA vaccines against COVID-19, our research into mRNA-based therapies spans over a decade and encompasses a variety of conditions5.

Collaborative Preclinical Studies

Our recent collaboration with University College London (UCL) marks a significant stride in exploring mRNA's role against rare diseases. A study conducted alongside scientists from UCL and King’s College London assessed mRNA's efficacy in combating argininosuccinic aciduria, a rare genetic disorder, in a preclinical mouse model.

This research, detailed in Science Translational Medicine, indicated that mRNA treatment could alleviate the fatal impact of the disease in mice. Survival extended beyond three months in treated mice, compared to untreated ones that succumbed within two weeks of birth. Importantly, a notable survival rate was observed in mice receiving mRNA as a rescue treatment6.

The Journey from Preclinical to Clinical

Argininosuccinic aciduria, occurring in roughly one in 100,000 newborns, disrupts protein metabolism, potentially causing elevated blood ammonia levels6. While these preclinical findings offer insights, it's crucial to emphasise the significant leap required to transition from animal models to human applications. The process is fraught with challenges, and successes in preclinical stages do not guarantee clinical efficacy in humans.

Moderna is aiming to make exactly this leap, having initiated human trials to further evaluate mRNA therapies for rare metabolic disorders, including propionic and methylmalonic acidaemias, which are ongoing in international clinical studies.

The preliminary nature of these findings highlights the essential, yet tentative, nature of preclinical research. Collaborations between pharmaceutical companies and academic institutions are vital in advancing scientific understanding. However, the translation of this research into effective human treatments remains uncertain7, underscoring the importance of cautious optimism in the journey towards developing new therapies for rare diseases.

UK-MRNA-2400018 Date of preparation February 2024


  1. Rare Diseases. Rare Disease Day: Frequently Asked Questions. Available at: https://rarediseases.org/wp-content/uploads/2019/01/RDD-FAQ-2019.pdf. Last accessed February 2024.
  2. University College London. mRNA technology could be possible treatment for rare diseases. Available at:  https://www.ucl.ac.uk/news/2024/jan/mrna-technology-could-be-possible-treatment-rare-diseases. Last accessed: February 2024.
  3. Pardi N, Hogan MJ, Porter FW et al. mRNA vaccines — a new era in vaccinology. Nature Reviews Drug Discovery 2018; 17; 261–279. Available at: https://www.nature.com/articles/nrd.2017.243. Last accessed February 2024.
  4. Riggs P. What is mRNA? The messenger molecule that’s been in every living cell for billions of years is the key ingredient in some COVID-19 vaccines. The Conversation. 2021. Available at: https://theconversation.com/what-is-mrna-the-messenger-molecule-thats-been-in-every-living-cell-for-billions-of-years-is-the-key-ingredient-in-some-covid-19-vaccines-158511. Last accessed February 2024.
  5. Moderna. About us. Available at: https://www.modernatx.com/en-GB/about-us/our-story. Last accessed February 2024. 
  6. Gurung S, Timmermand OV, Perocheau D et al. mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria. Sci Transl Med 2024; 16(729). Available at: https://pubmed.ncbi.nlm.nih.gov/38198573/. Last accessed February 2024.
  7. Norman, GV. Limitations of Animal Studies for Predicting Toxicity in Clinical Trials. JACC Basic Translational Science 2019; 4(7), 845-854. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978558/. Last accessed February 2024.



  • Rare diseases

Last modified: 08 May 2024

Last reviewed: 08 May 2024