Self-Amplifying RNA Engineering: a New Weapon against Cancer

RNA molecular engineering enables the design or modification of RNA molecules to make them perform specific biological functions. Many innovative cancer therapies are developed at this fascinating microscopic scale, through the integration of several disciplines, including biology, chemistry, and engineering. Still relatively unknown, self-amplifying RNA (saRNA) is a promising technology that is rapidly gaining momentum at the Université de Sherbrooke Cancer Research Institute (IRCUS).

RNA-based therapies attract a growing interest in oncology as they open transformative prospects for cancer treatment. A particularly innovative therapeutic approach relies on self-amplifying RNA (saRNA), i.e., able to replicate itself within cells. This technology paves the way to even more effective and better tolerated treatments for people living with cancer.

RNA, much more than a hero of the pandemic

Contrary to the popular belief, the therapeutic use of RNA is not a technology that emerged from the pandemic emergency; the latter simply revealed it to the general public. Scientists were working with this molecule long before the messenger-RNA (mRNA) vaccines against COVID-19 propelled it into the spotlights. mRNA is one of the forms of RNA that plays a key role, as it carries the information – the recipe – for making the proteins that are necessary for the proper functioning of the body's cells.

With scientific advances in molecular engineering, it is now possible to produce synthetic mRNA, which is then encapsulated in a lipidic nanoparticle (acting as a carrier) that allows it to enter the cell. Once inside, the conventional mRNA produces a protein – an antigen – which stimulates the immune system to fight off the intruder. The conventional mRNA vaccines against COVID-19 contain only the instructions to produce an antigen.

IRCUS is a particularly fertile environment for the development of RNA-based therapies; this is what prompted the young Professor and Researcher Taha Azad to settle in Sherbrooke to pursue his research programme on saRNA.

saRNA: an ally for tomorrow’s immunotherapy

Therapeutic saRNAs fall into the field of immunotherapy when they are used to stimulate the immune system against cancer cells. The anticancer applications of saRNAs are numerous and promise to push the boundaries of immunotherapy by overcoming the challenges that still hinder its effectiveness for many patients today.

They can be designed as personalized therapeutic vaccines, by adding instructions to specifically eliminate patient's cancer cells by targeting their neoantigens – unique proteins produced by cancer cells – that are absent from healthy cells. These tailor-made vaccines enable the body's immune system to spring into action and “heal” itself.

saRNAs can also serve as a vector for producing, directly in cancer cells, immunotherapy treatments or immunostimulatory proteins designed to locally strengthen the anti-tumour immune response.

mRNA is good, but saRNA is better!

2020 marked a turning point with the first human clinical trial using an saRNA vaccine. Like conventional mRNA vaccines, saRNA vaccines can be used to train the immune system, but with enhanced efficacy since they also contain instructions to replicate themselves once inside the cells.

This self-amplification capacity enables prolonged protein production, which improves the immune response while reducing the required doses. One can thus envision the full therapeutic potential of saRNA.

From Mexico to Sherbrooke: the inspiring journey of a student at IRCUS

At IRCUS, every research project reflects the passion and determination of a student whose journey is worth telling. Abril Muñoz's journey is a fine example. After studying biotechnology engineering at ITESO University, she left Mexico to pursue a master's degree in microbiology at the University of Sherbrooke, and more specifically at IRCUS.

Driven by her interest in cancer research, she traded the sunshine of her native country for the snow in Quebec, determined to build a career in what she describes as a wonderful environment.

Her master's project is divided into several successive stages. The first step involves producing saRNAs, from four different viruses having this self-amplifying mechanism, that will generate key proteins to activate the anti-tumour immune response and optimise their entry into cancer cells in culture (in vitro) by testing various lipid nanoparticles.

This protocol must subsequently be optimised for application in an in vivo cancer model, enabling preclinical validation for aggressive breast and brain cancers. This will enable us to determine whether the manufactured saRNAs can stimulate an effective anti-tumour immune response, leading to the elimination of cancer cells.

This project aims to develop therapies that harness the human body's natural defences — the immune system — to fight cancer.

Every day at IRCUS, we do our best to develop better therapies for cancer patients, with fewer side effects and increased efficacy, emphasises Abril Muñoz.

Immunotherapy has revolutionised cancer treatment, but many major challenges remain, including the low response rate of several cancers leading to treatment failure. The coming years will be crucial for the development of saRNA-based therapies. This flexible tool paves the way for truly personalized cancer treatments, a major advantage for those affected by the disease.

This is not science fiction, but a revolution on our doorstep: clinical trials are underway in the United States to test standard immunotherapy in combination with personalized saRNA vaccines against breast and colon cancers.

About Taha Azad
- Professor at the Department of Microbiology and Infectiology of the Faculty of Medicine and Health Sciences at Université de Sherbrooke.
- Professor and Research at the Université de Sherbrooke Cancer Research Institute (IRCUS)
- Researcher at the Centre de recherche du CHUS (CRCHUS)

A research that grows 10x!
It is not by chance that the Université de Sherbrooke stands out in research. Its secret? The judicious marriage of partnership, mutualization and interdisciplinarity: three strengths that now drive its recognition. Learn more on what propelled UdeS among the most prolific research universities in Canada.