What is mRNA?

Messenger RNA, or mRNA, plays a fundamental role in human biology, transferring the instructions stored in DNA to make the proteins required in every living cell. mRNA provides instructions to cells to make protein. Moderna’s approach is to use mRNA medicines to instruct a patient’s own cells to produce proteins that could prevent, treat, or cure disease. We are also working to advance the development mRNA therapeutics that restore the activity of missing enzymes responsible for various rare diseases, such as methylmalonic acidemia (MMA) and propionic acidemia (PA).

Dr. Stephen Hoge, Moderna President and Paolo Martini, Chief Scientific Officer discuss how Moderna is delivering on the promise of mRNA therapies for rare diseases

Hear from Dr. Tal Zaks, Moderna’s Chief Medical Officer and Lin Guey, Senior Director, Rare Diseases explain what mRNA-3704 is and how it may help patients with MMA.

Learn more about Moderna is working to change the future for patients with rare metabolic disorders.

mRNA and Rare Diseases

There are approximately 7,000 rare diseases that affect more than 300 million people worldwide. An estimated 30 million people in the U.S. are living with rare diseases, or 10 percent of the U.S. population. Yet, despite this high prevalence, there are approved drugs for only 5 percent of rare diseases and disorders.

Moderna recognizes the impact of rare diseases on patients and their families, particularly when the disease lacks any effective treatment options. We are advancing mRNA-based therapeutics with the goal of one day bringing treatment options to patients and their families.

A large number of diseases, including many rare genetic diseases, are caused by defects or deficits in proteins made by liver cells. By delivering mRNA therapeutics intravenously (IV), we can potentially stimulate production of therapeutic proteins in the liver in ways that cannot be achieved with other technologies. As such, rare liver diseases are our primary initial focus area.

Clinical Development Program

At Moderna, we are driven by our mission to deliver on the promise of mRNA science to create a new generation of transformative medicines for patients. We are currently advancing mRNA development candidates to address serious unmet needs across several therapeutic areas and multiple diseases. Clinical (human) trials are now underway for several of our investigational mRNA vaccines and therapeutics.

Below is a list of rare disease clinical trials for which Moderna is actively recruiting participants. We have provided links to the study listings on clinicaltrials.gov, where you can find more information, including details on eligibility criteria and clinical trial locations. For a full list of clinical trials enrolling for our investigational mRNA vaccines and therapeutics, please click here.

mRNA-3704 and Methylmalonic Acidemia (MMA) Program

The Phase 1/2 study will evaluate the safety of mRNA-3704 as well as its effectiveness in children 1+ years of age with MMA who have not received a liver or kidney transplant. Up to 34 patients with MMA are expected to take part in the study in multiple research institutions throughout the United States. Clinical trial sites are open in the U.S. and are expected to open in Europe as well. Learn more on clinicaltrials.gov.

MMA and PA Natural History Study

In support of the overall development program for MMA and PA mRNA investigational medicines, Moderna is conducting a natural history study to characterize the signs and symptoms of patients with MMA and PA. The goal of the natural history study is to help us better understand these disorders and characterize the broad population of individuals affected with MMA and PA. Learn more on clinicaltrials.gov.

mRNA-3927 and Propionic Acidemia (PA) Program

In September 2019, the U.S. Food and Drug Administration (FDA) completed their review of the Investigational New Drug (IND) application for mRNA-3927, Moderna’s investigational mRNA therapeutic for PA and allowed it to proceed to clinic. Moderna plans to initiate an open-label, multi-center, dose escalation Phase 1/2 study of multiple ascending doses of mRNA-3927 in patients with PA in the U.S. and Europe. Learn more here.

Frequently Asked Questions

  1. What is Moderna’s approach?
    Inherited metabolic disorders occur when a genetic mutation leads to a missing or dysfunctional version of a protein that is important for metabolism. While certain lifestyle changes, like dietary restrictions, may help alleviate the most severe symptoms, there are no treatments for the underlying genetic cause for many of these disorders. Moderna is working to address this underlying cause by providing new instructions to cells so the body can replace these missing or dysfunctional proteins. These instructions are known as messenger RNA or mRNA. Our cells use mRNA to interpret information passed down through our genes and turns this information into proteins that build or regulate our bodies. Moderna’s approach is to give specially engineered mRNA to provide new instructions to the protein-making machinery already inside the cell to treat the underlying cause of inherited metabolic disorders and other diseases. We believe mRNA therapeutics and vaccines have the potential to work beyond what’s possible with today’s small molecules (or pills), biologics and vaccines. As of September 2019, we have 14 programs in clinical studies across different areas such as infectious diseases, immuno-oncology, rare diseases and cardiovascular diseases, and more than 1,300 clinical trial participants have been dosed with our mRNA technology. Some of these programs are being led by our team and others are being developed in collaboration with Merck and AstraZeneca.

  2. How does mRNA differ from gene therapy?
    Helping the body make its own medicine using mRNA sounds like it might be similar to gene therapy or gene editing. While these treatment approaches seek to treat disease through genetic information, they take fundamentally different approaches. Gene therapy and gene editing alter the original genetic information each cell carries. The goal is to produce a permanent fix to the underlying genetic problem by changing the defective gene. Moderna is taking a different approach to address the underlying cause of MMA and other diseases. mRNA transfers the instructions stored in DNA to make the proteins required in every living cell. Our approach aims to help the body make its own missing or defective protein. Unlike gene editing and gene therapy, mRNA technology does not change the genetic information of the cell, and is intended to be short-acting. It acts like traditional drugs that can be adjusted over time based on the dose and frequency needed. In simple terms, we are working to provide physicians and patients with a “controllable” way to start and manage their therapy over time.

  3. What regulatory designations do mRNA-3704 and mRNA-3927 have?
    The FDA has granted Fast Track designation to both mRNA-3704 and mRNA-3927, which is provided to facilitate development of drugs designed to treat a serious or life-threatening condition and fill an unmet medical need. The programs have also received Rare Pediatric Disease Designation by the FDA and Orphan Drug Designation by both the FDA and the European Medicines Agency (EMA).

    The FDA grants Orphan Drug and Rare Pediatric Disease designations to products deemed to be promising for rare diseases to further advance their scientific development. Similarly, the EMA grants Orphan Drug Designation to facilitate the development and authorization of medicines for rare diseases.

  4. What research has been done on mRNA-3704?
    The animal data evaluating our mRNA study drug targeting methylmalonic acidemia (MMA) are compelling. We recently published data evaluating our mRNA study drug in mouse models of methylmalonic acidemia (MMA), which were developed at NIH. In other words, in mice that have a form of MMA, our study drug substantially improved survival and led to sustained growth with long-term dosing and no safety concerns were observed.

  5. What is required of me/my child to participate in the Phase 1/2 trial?
    For inclusion and exclusion criteria, please visit clinicaltrials.gov and talk to your physician.  

  6. Can I participate in other clinical trials in the future if I participate in Moderna’s mRNA-3704 Phase 1/2 trial?
    Moderna cannot advise on future clinical trial participation. Please refer to clinicaltrials.gov for clinical trial eligibility.  

  7. Where can I find more information on MMA or PA?
    You can find more information on MMA or PA at the websites below or consult with your physician.

    Organic Acidemia Association (OAA)
    PA Foundation
    National Organization for Rare Diseases (NORD)
    Metabolic Support UK
    NIH Genetics Home Reference: MMA
    NIH Genetics Home Reference: PA

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