Five questions on pseudouridine, with Matthew Thompson

Press releases are necessarily short, so we like to go a little deeper into our latest news for those who are curious. Matthew Thompson, head of enzyme development and innovation at EnginZyme, explains why synthesizing pseudouridine is big news for us.

What is pseudouridine and what does it do to make vaccines better?

Pseudouridine is a naturally occurring modified nucleoside. In the context of RNA, pseudouridine is often dubbed the “fifth nucleotide.” It’s a modified form of uridine, which plays a role in the function and stability of RNA. Incorporating pseudouridine into RNA-based vaccines can increase their efficacy and reduce the chances of side effects. It’s a bit like a turbo charger for mRNA vaccines.

Why is your method so much cleaner and better than the old way?

Traditional methods of synthesizing pseudouridine often involve multiple steps, chemicals, and generate quite a bit of waste. Our enzymatic approach is more streamlined. It’s like the difference between a petrol car and an EV. Not only does it produce way less waste, but it’s also more environmentally friendly and cheaper to run.

What could this lead to in terms of other pharma-related business for EnginZyme?

The horizon looks promising for EnginZyme. Beyond pseudouridine, there’s a burgeoning interest in other, similar raw materials, especially modified nucleotides. Given our expertise and the technology we’ve honed, EnginZyme is perfectly poised to pioneer the scalable manufacturing of these nucleotides and other crucial raw materials for mRNA production!

Why is it called ‘pseudo’ — doesn’t that mean fake?

Ha, I completely get why you’d think that! The term “pseudo” does often imply something fake, but in this context, it’s more about the structure. Pseudouridine is made of the same constituent parts as uridine, but one part of the molecule has been moved around a bit. It’s a bit like an RNA doppelgänger.

What led to your team’s discovery of the enzymatic process to synthesize it?

Like so many scientists during the pandemic, we were on the lookout for opportunities to truly make a difference. We weren’t just sitting idle; we wanted to contribute and make an impact both in that moment and for the future. That’s when the “pseudo” opportunity (pun intended!) caught our eye. We realized that our technology could significantly improve the raw materials part of manufacturing mRNA vaccines. So, we dived deep into the world of these raw materials, eventually leading to our development of the enzymatic process to synthesize pseudouridine. It’s been a rewarding jump into a new space for us.