The flow of genetic information is an essential process in biology that involves the transfer of genetic material from DNA to RNA to proteins. At the heart of this process is a molecule called messenger RNA (mRNA).
Without mRNA, cells would not be able to create the proteins necessary for various cellular processes, and genetic information would not be able to flow from the nucleus to the cytoplasm.
This article discusses what mRNA is and its role in molecular biology.
Defining Messenger RNA
Messenger RNA is a ribonucleic acid (RNA) molecule that plays a central role in the flow of genetic information in cells. mRNA molecules are transcribed from DNA in the cell nucleus and carry the genetic information encoded in the DNA to the ribosomes, the cellular organelles responsible for protein synthesis.
The mRNA molecule is a single-stranded RNA molecule complementary to the DNA sequence from which it was transcribed. The sequence of the mRNA molecule is determined by the order of nucleotides in the DNA template strand, with each three nucleotides, called a codon, corresponding to a specific amino acid. The sequence of amino acids, in turn, determines the sequence of the protein that will be synthesised.
mRNA synthesis is initiated by binding an enzyme called RNA polymerase to a specific region of the DNA called the promoter. The RNA polymerase then unwinds the double helix structure of the DNA and begins transcribing the DNA sequence into a complementary mRNA molecule. As the mRNA molecule is synthesised, it is processed to remove non-coding regions called introns and join the coding regions, called exons, to create a mature mRNA molecule.
The mature mRNA molecule is then exported from the nucleus and travels to the cytoplasm, where it binds to ribosomes. The ribosome reads the sequence of nucleotides on the mRNA molecule in groups of three, each corresponding to a specific amino acid. As the ribosome moves along the mRNA molecule, it synthesises a protein by joining its amino acids in the order specified by the mRNA sequence.
mRNA in Therapeutic Intervention
Messenger RNA has become an essential tool in therapeutic intervention due to its ability to control protein expression and serve as a template for the production of specific proteins. mRNA-based therapies offer several advantages over traditional protein-based therapies and small molecule drugs.
First, mRNA-based therapies are highly specific, encoding the exact protein of interest. This specificity allows for targeted therapies that selectively block a disease-causing protein’s activity or replace a missing or defective protein.
Second, mRNA molecules are rapidly degraded in cells, allowing for precise control over the protein expression level. This feature makes mRNA-based therapies more flexible and adaptable than traditional protein-based therapies, where the protein dosage can be challenging to regulate.
Finally, mRNA molecules can be modified chemically to improve their stability, increase their efficiency, and target them to specific cells or tissues. These modifications allow for greater control over the delivery and distribution of the mRNA molecule and its encoded protein.
One of the most significant advances in messenger RNA-based therapies has been the development of mRNA vaccines, such as the Pfizer-BioNTech and Moderna COVID-19 vaccines. These vaccines use mRNA molecules encoding the spike protein of the SARS-CoV-2 virus to stimulate an immune response against the virus.
The mRNA is encapsulated in lipid nanoparticles and delivered to cells, where it is translated into the spike protein. The immune system recognizes the protein as foreign and produces antibodies against it, protecting against infection.
Messenger RNA-based therapies have also shown promise in treating various diseases, including cancer, where they can be used to induce the expression of tumour-suppressing proteins or target cancer cells for destruction by the immune system. In one recent study, mRNA was used to encode chimeric antigen receptor (CAR) T cells, genetically engineered immune cells that target and destroy cancer cells. The mRNA-encoded CAR T cells were highly effective in killing cancer cells in vitro and in mouse leukaemia models.
mRNA-based therapies offer a powerful new disease treatment and prevention approach, potentially revolutionising medicine.
mRNA Use Cases
There are several use cases for mRNA-based therapies.
In a study published in Nature, researchers used mRNA to program immune cells to attack cancer cells. The mRNA encoded a chimeric antigen receptor (CAR) that recognized and targeted cancer cells. When the mRNA was delivered to immune cells in vitro, the resulting CAR T cells were highly effective in killing cancer cells. The researchers suggest that this approach could be used to develop personalised cancer immunotherapies.
Genetic Disease Therapy
In a study published in the New England Journal of Medicine, researchers used mRNA to treat a patient with cystic fibrosis. The mRNA encoded a functional copy of the CFTR gene, which is mutated in patients with cystic fibrosis. The mRNA was delivered to the patient’s lungs via nebulisation. The treatment improved lung function and reduced respiratory symptoms, suggesting that mRNA-based therapies could effectively treat genetic diseases.
The development of mRNA-based vaccines has been one of the most exciting recent applications of mRNA technology. The Pfizer-BioNTech and Moderna COVID-19 vaccines, which use mRNA to encode the spike protein of the SARS-CoV-2 virus, have been highly effective in preventing COVID-19 infection.
A study published in the New England Journal of Medicine found that the Pfizer-BioNTech vaccine was 95% effective in preventing COVID-19 infection in clinical trial participants.
These case studies demonstrate the potential of messenger RNA-based therapies in various applications, including vaccines, cancer immunotherapy, and gene therapy.
Risks With mRNA
Despite the promise of messenger RNA (mRNA) as a powerful tool for therapeutic intervention, there are several risks and challenges associated with its use.
One of the primary concerns is the potential for off-target effects, where the mRNA molecule produces unintended proteins or triggers an immune response against normal cells. This risk can be minimised through careful selection and design of the mRNA molecule and its delivery system, but it remains a significant challenge in developing mRNA-based therapies.
Delivering mRNA molecules to their target cells presents another challenge. mRNA is a large, hydrophilic molecule that rapidly degrades in the bloodstream and other extracellular fluids. Delivering mRNA molecules to cells is essential for their effectiveness in protein translation. Researchers have developed several approaches to overcome this challenge, such as utilising lipid nanoparticles to protect mRNA molecules from degradation.
Another risk associated with mRNA-based therapies is the potential for immune system activation or adverse reactions. Though these are generally mild and short-lived, mRNA vaccines have been associated with side effects such as injection site pain, fever, and fatigue. More serious adverse events have been reported in rare cases, such as anaphylaxis.
Finally, there is a risk that the rapid degradation of mRNA molecules in cells could limit the effectiveness of mRNA-based therapies. mRNA molecules have a relatively short half-life in cells, which could limit the duration of protein expression and the therapeutic effect. However, this risk can be mitigated by using modified mRNA molecules that are more stable or by administering multiple doses of the mRNA over time.
While mRNA-based therapies offer many exciting disease treatment and prevention possibilities, they also present significant challenges and risks. Careful consideration and planning will be required to maximise the potential benefits of mRNA-based therapies while minimising the risks.
However, recent case studies have demonstrated the potential of mRNA-based therapies in various applications, including vaccines, cancer immunotherapy, and gene therapy. The development of mRNA-based therapies represents an exciting frontier in biomedicine, with the potential to revolutionise how we treat and prevent disease.
Disclaimer: The information provided in this article is solely the author’s opinion and not investment advice – it is provided for educational purposes only. By using this, you agree that the information does not constitute any investment or financial instructions. Do conduct your own research and reach out to financial advisors before making any investment decisions.
The author of this text, Jean Chalopin, is a global business leader with a background encompassing banking, biotech, and entertainment. Mr. Chalopin is Chairman of Deltec International Group, www.deltec.io.
The co-author of this text, Robin Trehan, has a bachelor’s degree in economics, a master’s in international business and finance, and an MBA in electronic business. Mr. Trehan is a Senior VP at Deltec International Group, www.deltec.io.
The views, thoughts, and opinions expressed in this text are solely the views of the authors, and do not necessarily reflect those of Deltec International Group, its subsidiaries, and/or its employees.