Riding the New Wave

mRNA was an exciting field long before the pandemic accelerated its development. But now that the field has found a new level of success, how can it apply its learnings to improve treatment options for other diseases? Igor Splawski, Chief Scientific Officer of CureVac, shares his thoughts on what we can look forward to – if we keep the wheel turning.

How did you become interested in mRNA-based therapeutics?

It feels like I’ve always had an interest in discovering the genes behind diseases and disorders – certainly, it was the focus of my work starting with my PhD in 1992. I continued my gene identification research after the completion of my doctorate at the Howard Hughes Medical Institute, Children’s Hospital Boston, and Harvard Medical School, where I became an assistant professor.

In 2005, I joined Novartis. While using the learnings from human genetics, I completely switched my focus to biologics. Most of my years there were spent working on ophthalmology and cardiovascular disease. Towards the end of 2011, I reignited my former interest – my “unfinished business” – by starting a group specializing in mRNA. The group began with one person but, at its peak, numbered around 50. Our primary goal was gene replacement with mRNA, where we showed several proof-of-concept studies in vivo and expression in non-human primates. Moreover, that’s when I met some of my current colleagues from CureVac – the first ever mRNA technology company, founded in 2000 with the aim to successfully harness mRNA for medical purposes.

Last July, CureVac hired me as their Chief Scientific Officer. The work has proved extremely satisfying. To me, few things are more rewarding than working at the edge of knowledge in a whole new field of science, knowing and seeing that our work makes great contributions to health, medicine, and society.

Pre-pandemic, what were industry attitudes towards mRNA?

Prior to the onset of the pandemic, mRNA wasn’t widely known. It appeared to be falling in line with gene therapy research. Certain scientific leaps helped change this. The discovery of small interfering RNA (siRNA) by Andrew Fire and Craig Mello was a key milestone – the Nobel Prize they won for it highlighted the importance of RNA to a wider audience. This was cemented in 2013 and 2018 with the approval of the first antisense oligonucleotide and siRNA drugs, respectively, compounds that directly affect mRNA.

While these achievements were incredibly significant, it is the COVID-19 pandemic that brought mRNA to the fore. Tens of millions of individuals around the world have now been vaccinated with the first two vaccines approved for emergency use. The Pfizer-BioNTech mRNA vaccine was recently fully approved for use by the FDA. But what was most stunning about this newfound success was the speed – in part driven by technological development, and in part by the worldwide need for safe, effective vaccines. The field is now exploding – in the last year, we have seen the launch of scores of mRNA biotechnology companies. Larger players have initiated efforts of their own, and in some cases are acquiring mRNA companies to jumpstart the process.

How do you think mRNA research will evolve post-pandemic?

Most mRNA trials before COVID-19 involved only a small number of individuals. Now, millions have been vaccinated with mRNA. The push to make this happen produced a great deal of research and learning. We have the opportunity to capitalize on the work, and explore all kinds of interesting applications based on the data we have acquired.

Though many companies will continue to explore infectious diseases, new data can and will be used to develop cancer vaccines and treatments for indications where there is a need to express intracellular proteins, inhibitors, or modulators.

“Disruption” is a hard buzzword to avoid; mRNA therapies have certainly changed the industry for good. The fact that more people are getting involved is exciting; outsiders are now joining the field, and industry veterans are learning from them. We can expect input from engineers and physicists, sociologists and ethicists, chemists and IT experts – all will have a say in the future direction of the field. These collaborations are so important because they connect us to forward-thinking minds outside the pharmaceutical industry. There is scientific talent in other industries that we can tap into and help grow (and vice-versa!).

And how is your work informing the future of the field?

COVID-19 remains a priority for us at CureVac. We are continuing to work on our current vaccines. We have already seen significant improvements in our second-generation product. We are also looking into the application of mRNA technology to the treatment of cancer, as well as rare diseases. We have interest in the eye and lung, as well as other organs with applications that might differ depending on the indication that they’re trying to address, and the medical need.

With our partners, such as GSK and the Bill and Melinda Gates Foundation, we are working on other infectious diseases. We are taking the learnings from the prophylactic vaccines into therapeutic vaccines, e.g. the use of mRNA vaccines for the treatment of cancer. There is only one approved cancer vaccine now – it’s a very complicated indication. By the time cancer is diagnosed, in most cases it has already turned into many diseases that can hardly be treated with one approach. It is my hope that mRNA can make a great difference here, either alone or most likely in combination with alternative types of approved treatments, including antibodies, low molecular weight compounds, as well as cell therapies.

My colleagues and I are excited about mRNA’s application to the treatment of rare diseases. Personally, this is where most of my interest lies – likely because of my 30 years of experience working on genetics and human disease.

How else will the field continue to grow?

I think the biopharmaceutical industry is courageous. And much of the courage comes from smaller companies that are usually founded on an idea and vision. It is those ideas that can take exciting new forms, or reach places not previously explored. It takes fortitude and hard work by pharmaceutical companies to bring out this species of innovative disruption. The pull from the medical field and the understanding of new technologies by society and regulators are quite important as well.

Here’s another exciting thing that pharmaceutical companies need: new talent. Pharma and other tech industries need today’s young people to return to sciences. In recent years, it seems there has been a drift away from science. But I want young people to know there will always be fulfilling jobs in all fields of science, combined with the thrill that discovery ignites. Of course, I’m biased, but I believe that nothing else compares to the excitement of science and medicine, and their contribution to society. Teachers, professors, and educators at every level are the other necessary and amazing contributors to society’s development and advancement.

What can institutions do to encourage more students to pursue higher education in science?

One example I can give you is my own daughter. She now studies physics, but not because I am a scientist. Years ago, my children made it abundantly clear they weren’t interested in listening to my pro-science career advice! So, her decision came as a surprise to me. She had chosen to pursue the subject because of an inspiring teacher at her school. The daughter of a friend of mine completed a degree in physics, and is working on her PhD in astronomy. I was stunned to hear from her, in retrospect I should not have been, that she too was inspired by the same teacher! This is one area where we can make a difference- educate, encourage, and reward competent and productive teachers.

Besides teaching, there is storytelling. We have to write and tell stories that interest and inspire young people, and show the realm of possibilities within science. We should encourage reading, and not forget that many young people use YouTube and other media platforms as learning tools – so we should try to engage with them in ways that are fun and relevant to them.

It is true that educators, peers, and passions play a huge role in dictating our life choices, but to keep young people in science we have to play an even more active role in showing them how vibrant academic and industry research is.

What scientific discoveries have thrilled you lately – and where do you foresee the next?

There are problems in physics that vexed people for over 100 years that were solved in the last one or two decades. The first siRNA drugs were approved just three years ago. Now, the first mRNA drugs are approved. Consider these are whole new classes of medicine! If people don’t yet find this exciting, I hope they stumble across an article, teacher, or a friend that charms them with this knowledge and changes their minds.

Great discoveries come to those who work and think hard, and some things come as a bonus – and from places you’d never expect. Conversely, exciting discoveries don’t happen on a daily basis. Sometimes there are times where one sees a period of negative results; notably, these should be viewed as something worthwhile and temporary, and we can share such learning experiences with younger scientists, so that they are not easily discouraged when the first signs of difficulty appear.

To me, discovery in life science comes in waves – there are peaks and troughs. People should enjoy riding the crest of the wave, and endure the ups and downs that come with waves. My own career has been enormously rewarding – and not because every success was easily won but because of the experience of discovering genes and drugs, because of the amazing people that I have learned from, worked with, and met along the way. I hope many more people choose science with the understanding that not everything can be discovered in one day, it is a long journey.

Of course, it's not an easy! However, the satisfaction that comes with discovery and pushing the boundaries of human knowledge make the journey so very invigorating, exhilarating, and deeply rewarding.