Taking a frothy risk to advance gene therapy – Fred Hutchinson Cancer Center

Inspiration sparked by shaving

Stephan co-founded Tidal Therapeutics to help commercialize his immune-cell programming nanoparticles (acquired by Sanofi in 2022). His lab needed a new direction, and inspiration struck one morning as he watched his freshly sprayed shaving foam expand in his palm.

I thought, Let's explore foam, Stephan said. Maybe we can make a formulation of foam that is not like the foam in in our shaving foam, but something that is biocompatible, to deliver therapeutics.

The froth had properties that would be attractive in a drug-delivery vehicle. Its volume started small, but puffed up. The foam stayed where it was sprayed, and didnt slide away. These characteristics could help get a therapeutic into contact with more critical cells while also ensuring that it didnt slip away.

Trying new substances or approaches that come from things in everyday life that you wouldn't necessarily associate in medical applications is sometimes a really interesting way to drive down costs and deliver drugs more easily, Fitzgerald said. But it was definitely a little bit out of my wheelhouse.

Foam-as-medical-delivery method isnt without precedent, Stephan noted. Foam-based delivery already enhances certain applications like delivery of hemorrhoid medication and intra-uterine imaging.

But could foam enhance gene therapy?

To create a bio-compatible foam, Stephan and his team initially took inspiration from the food industry.

Cocktails, ice cream, yogurt: they know how to make things foamy, he said.

Stephan Lab members, including staff scientist Sirka Stephan, PhD, started experimenting with ingredients available from the pantry store, he said.

Importantly, these materials are dead cheap, Stephan said. Theyre available for pennies. Theyre manufactured at large scale, and because theyre already used for pharmaceutical applications like coating tablets theyre available pharmaceutical-grade.

The scientists formulated a solution of methylcellulose (a food binder) and xanthan gum (a food thickener) that, when aerated using two lab syringes, bubbles into an easy-to-apply froth.

But did it have the potential to improve gene therapy?

We started with a lot of hypotheses in terms of, could foam potentially concentrate our gene therapy, keep it more localized, and help it stay in the tissue where we wanted to adhere? Fitzgerald said. My job was to do the experiments to prove the hypotheses.

Foam has certain properties that make it an attractive drug-delivery vehicle. Its more than tightly packed air bubbles: In a foam, the bubbles are separated and surrounded by incredibly thin layers of continuous liquid, called lamellae. Active ingredients become highly concentrated in these lamellae, which allows foam to deliver highly concentrated doses of medicine to large areas, even if the total dose is small.

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Taking a frothy risk to advance gene therapy - Fred Hutchinson Cancer Center