Written by Charles Leach, Edited by Caroline Babisz and Natasha Barrow.

Synthetic biology has grown tremendously popular in recent years, following successes from the realms of gene therapies to sustainable agriculture and much more. Our next guest on the SEC series truly embodies the ‘dogma breaking’ aspect of synthetic biology, targeting the inside of our cells through their start-up NanoSyrinx.

The company philosophy is centred around the manipulation of a cell’s interior and how that can be harnessed to yield lifechanging medicines. We sat down with Joe Healey, Founder & CEO, to learn a bit more about their journey and the new subfield of science he is driving.

“Great to have you on the series Joe. Tell us a bit about your background..”

Great to be here. I’ve been fortunate to follow a particularly interesting area of science from its inception in a Master’s program at Warwick University, all the way to our successful company spin out in NanoSyrinx. Stumbling across Nick Waterfield’s lab as a young scientist, I quickly learnt about the strange wonders of Photorhabdus bacteria that produce toxin-like structures we call ‘nanosyringes’. The rest from there has been a blend of incredible science, inspiring people to work with and a stroke of good fortune.

“We are interested to hear about that blend, tell us more”

Whilst I was studying my PhD, our obsession became understanding more about these bacteria, their nanosyringe structures and the application of these structures in biology:  their function, their intra-species differences, their use to the host bacteria and ultimately, how they could be used for human benefit.

We discovered the original nanosyringes in nature – in an unusual bacterial species most will be unfamiliar with. Through studying their lifecycle we discovered that the bacteria produce these fascinating syringe-like structures which contain a wide variety of protein payload molecules, each having different functions. The bacteria release the syringes and use these to manipulate host organisms that they are trying to infect, for example, by dampening down the immune system.

Figure 1: 3D diagram demonstrating the release of payload into target cells.

Around halfway through my PhD, Warwick Ventures attended one of our Friday group meetings. This kickstarted a conversation with them, where we described the nanosyringe structures and how we believed they could be used to deliver specific payloads into cells. They saw that if these payloads could be replaced with a therapeutic, we could be onto a breakthrough, so this was really the green light to get us going. The Warwick tech transfer officer at the time, James Lapworth, has since been hugely influential as our Chief Business Officer.

“Starting out your company journey during your PhD, was there anything that made you feel out of depth at such an early age?”

Not particularly. Everything was a new challenge and I enjoy learning by doing so I viewed it as having nothing to lose and everything to gain.  For example, on graduating my PhD, I went straight into the Innovate UK ICURe program, which I would thoroughly recommend to any budding PhD grad working with a smart technology.

Here, you essentially embark on a 3-month funded fact-finding mission with ~100 academic and industry key opinion leaders (KOLs), to pressure test your idea against its market potential. I was fortunate to gain valuable insight from every conversation I had, and then take those learnings to conversations with future investors later on.

“This was a fantastic introduction to navigating those conversations and validating our approach without the high stakes [to be later faced with investors].”

“Tell us a bit more about the technology. What makes it special?”

The premise of NanoSyrinx’ science is rather peculiar. People tend to either understand it straight away or not all. The tech is similar to a bacteriophage, which people connect with fairly quickly if they have a microbiology background, but obviously that’s not everyone.

Figure 2 – molecular level schematic of NanoSyrinx’s Nanosyringe technology.

As mentioned earlier, the bacteria produce the syringe-like structures which can contain a wide variety of payload molecules.

Where we apply our innovation is in engineering the genetics that produce, modify, and load the nanosyringes so that they can be used as precision medicines. The nanosyringe is comprised of a plasmid of around 30kilobases, containing all of the genetics necessary to express, assemble and load the nanosyringes in a functional way.

What NanoSyrinx focus on is changing the payload and engineering how the nanosyringes interact with the target cell.

Our synthetic biology value proposition is simple; each component of the 30kb backbone can feasibly be engineered, giving us exquisite control over vehicle properties, payload content, and cell selectivity.

“I think I’m following.. so what constitutes the payload and how do you localise it?”

The payload is packaged alongside the nanosyringe vehicle. The 3 major steps to do so are:

  • Step 1: Construct Design
  • Step 2: Fermentation
  • Step 3: Purification

In parallel, we made the modifications required to target a specific cell type. A few years back, during my PhD, we identified the appropriate gene/protein that is responsible for binding, and the region(s) within that require editing. By modifying these proteins at the first step, in concert with the payloads, we can yield re-targeted, re-loaded nanosyringe vehicles for purification. Looking at the schematic above, you’ll also see an ‘arm like’ protein which interacts with the cell surface. We identify the highly variable region at the end of the nanosyringe arms to bind to different cell surfaces of different tissues in the body, much like an antibody does.

This can then be delivered to a variety of patient populations.

“The technology sounds relatively simple but highly targeted. What patient populations are NanoSyrinx’ primary focus?”

To date, we have been developing the synthetic biology platform to the best of its ability whilst remaining therapeutic agnostic. More recently, ahead of our Series A fundraise, we have started to ‘shift gear’ toward mapping out various therapeutic areas where we feel we can provide the most benefit or offer something unique. The versatility of the technology almost makes it a blessing and a curse to offer so much value across various diseases, but with focus we’re achieving more targeted results, so we are honing in on a few select areas where we will make the biggest impact.

Figure 3: Potential applications of NanoSyrinx’s technology.

Ranging from oncology to longevity to metabolic diseases, the possibilities really are boundless. We are also exploring the possibility of non-therapeutic uses, for example, as tools for gene therapy delivery as an alternative to the current industry standard of viral vectors.

“It sounds like you’ve made huge progress in the past 3 years. What are your proudest achievements?”

That’s a tough one.. but there are 3 stand outs:

  1. Building such a passionate team with leading scientific credibility. For example, Marie joining as CSO from a senior research role at GSK and non-executive directors with huge gravitas in our community.
  2. Raising our over-subscribed seed round over 50% in excess of our goal sum. This surprised us as much as anyone but validated our scientific hypothesis and our combined efforts that built it.
  3. Winning the AbbVie Golden Ticket and gaining insight from senior figures at the company. This has already proved valuable towards our business strategy.
Figure 4 - NanoSyrinx, AbbVie & Pioneer Group's golden ticket winners 2022. This recognition of excellence provided 1 years’ free lab space, tailored support from AbbVie’s world leading research team and exclusive access to their networks.

“These are 3 succinct milestones that have clearly come from years of dedication. In that time, what unique feature of NanoSyrinx enabled them?”

If I had to pick one feature, it has to be our technology. The underlying IP is genuinely like nothing else seen before, not just novel application, genuinely novel by its own identification. We know this through our humble beginnings where we had little to no data to speak of, but people still took our ideas very seriously. That’s the transformative potential this technology has, so if disruption is your scientific niche then come and get involved – we’re on a growth mission in the next 3 years!

“Lastly Joe, that big picture question: what would you advise someone else in your position 3 years ago?”

Have confidence & faith in what you’re doing and seek to surround yourself with leading experts. Enroll on to accelerator & entrepreneurship programmes if possible, constantly pressure test your ideas and seek disapproval where you can, this all builds towards the best possible strategy and product.

But most of all, live & breathe what you do, and realise you’ve got nothing to lose & everything to gain!

If you’ve enjoyed reading and would like to learn more about NanoSyrinx or invest in their further journey, please get in touch with Joe directly at Joe@nanosyrinx.com


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