What is RNA and how is it used for therapeutics?

DNA is the blueprint of life. A nucleic acid that resides inside the nucleus of every cell, it carries the instructions for creating and maintaining our bodies. But how do these instructions become actual, functional parts of our cells? 

That’s where RNA, another nucleic acid, comes in. It plays a crucial role in translating DNA code into the building blocks that make up the proteins that keep us alive. Now, the properties of RNA are being used to power a scientific revolution in medicine, from vaccines to new disease-targeting therapeutics.

The diversity of RNA

There isn’t just one type of RNA molecule. It’s a diverse family, and each type has specific roles. Here are some of the RNA modalities that can be interacted with, modified or created synthetically in a lab for applications in pharma and medicine: 

• Messenger RNA (mRNA): Carries the genetic instructions from DNA to the ribosomes, the sites in a cell where proteins are made. 

• Transfer RNA (tRNA): Delivers amino acids, the building blocks of proteins, to the ribosomes. 

• MicroRNA (miRNA): Regulates how genes turn on and off by controlling the production of specific proteins. 

• Small interfering RNA (siRNA): Silences specific genes by triggering the breakdown of their mRNA. They are like the ​“off” switches for protein production. 

• Single guide RNA (sgRNA): These lab-made, synthetic RNAs are precise guides for genome editing technology, dubbed genetic scissors, sgRNA can be used by scientists to modify DNA with high precision. The 2020 Nobel Prize for Chemistry recognised the researchers who developed the technology called CRISPR/​Cas9.

• Self-amplifying RNA (saRNA): A type of synthetic mRNA that encodes an enzyme called replicase, which copies the original strand of RNA once it is inside the cell. This means a smaller dose of RNA can be used for higher protein expression and efficacy to treat disease.

Tailored tools for health/targeting disease

RNAs, including some of those mentioned above, can be manufactured as oligonucleotides to treat disease or infection. Oligonucleotides are short, synthetic pieces of RNA or DNA, designed to interact with specific RNA molecules inside cells. Imagine these ​“oligos” as a precise code pointing to a particular instruction in the vast library of DNA. 

Knowing that code is paramount to identifying the cause of diseases. And with advances in gene sequencing, we’re now able to ​“read” and ​“write” DNA or RNA faster and at lower cost than ever before. That opens a route to combating previously hard-to-treat or rare diseases. Oligos are powerful tools that can be used to do this in various ways, including: 

• Silencing genes: Certain oligos like siRNAs can bind to mRNA. This can block protein synthesis, effectively silencing faulty or harmful genes when targeted. Chemically engineered siRNAs have shown promise as potential treatments for Huntington’s disease models.

• Altering gene expression: Antisense-oligos (ASOs) can be used to change the mechanisms related to gene expression, offering a potential treatment for genetic diseases. Healthy copies of genes essentially replace faulty ones to reverse disease. They are already being used in the treatment of neurodevelopmental disorders like spinal muscular atrophy. 

• Triggering the immune system: Some oligos can be designed to mimic the DNA or RNA in viruses, resulting in mRNA vaccines that trigger the immune system to fight off infections. The mRNA vaccines developed during the COVID-19 pandemic saved millions of lives.

Producing RNA-based therapeutics

CPI is bridging the gap between research and commercialisation of RNA-based therapies. This includes developing efficient and reliable manufacturing processes for both oligonucleotides and the delivery systems needed to get them into cells. 

During the COVID-19 pandemic, CPI became a member of the UK Government’s Vaccine Taskforce, in which our key role was to develop mRNA vaccine candidates. We’ve since built on that legacy and experience by opening the dedicated RNA Centre of Excellence, an innovation centre with the capacity to deliver 100 million vaccine doses in the event of a future health emergency. The GMP-certified facility is currently the only open-access facility in the UK that can produce lipid nanoparticles for the safe and effective delivery of RNA vaccines and therapies. 

That expertise will be enhanced by the opening of the Intracellular Drug Delivery Centre, which has been established in a collaborative partnership with the Medicines Discovery Catapult, the University of Strathclyde, the University of Liverpool and Imperial College London. 

To make sure the UK continues to be at the forefront of RNA-based therapeutic technology we need to ensure that the future workforce has the required skills and knowledge. That’s why the RNA Training Academy has been established. 

We’re so passionate about the promise of RNA-based therapeutics that we created the RNA Vaccines and Therapeutics Conference in partnership with Imperial College London and The BioIndustry Association (BIA).

With the mRNA vaccine and therapeutics market predicted to be worth more than $68 billion by 2030, we’re working to ensure that the UK – and its thriving pharmaceutical industry – can continue to play a significant role in this growth.

Paving the way forward for RNA-based medicine

RNA-based therapeutics and vaccines represent a paradigm shift in healthcare, offering hope for treating – and potentially curing – previously untreatable conditions. New mRNA vaccines are currently under exploration, not just for viruses like the ones that cause COVID-19 or influenza, but also malaria and even cancer and other severe chronic diseases. The first CRISPR-based therapy, for sickle cell disease, has been approved for use in the UK and USA, setting the stage for a boom in gene-editing treatment. 

As research and development in this field continues to flourish, the potential for RNA-based therapeutics to improve and save lives is astounding.