Source: © Jeremiah Gassensmith

The MOF-Jet can fire gene therapies or vaccines directly into cells without the pain of a needle

A new method has been developed to deliver vaccines and biologics in a powdered form by encasing it in a metal–organic framework (MOF). This encapsulation also has the advantage that it stabilises pharmaceuticals meaning that no refrigeration is needed for drugs like vaccines. Researchers from the University of Texas at Dallas presented their work on this needleless MOF-Jet injector system, which is driven by compressed gas, at the spring meeting of the American Chemical Society (ACS) on 27 March.

The project was born out of pandemic boredom when its principal investigator, Jeremiah Gassensmith, was stuck at home during the Covid-19 pandemic. He decided to have some fun building a compressed gas-powered jet injector out of inexpensive components that he bought online.

‘We couldn’t even get toilet paper but I could still order parts,’ he recalled at an ACS briefing. ‘I wanted to build a thing that could shoot MOFs or salt or something into the skin – I wanted to develop a homemade “gene gun”,’ he said. ‘I just hit the internet and started doing some research, and I built this thing and was shooting table salt at aluminium foil, and just shooting salt around my home office.’

Eventually, the pandemic eased and Gassensmith brought the MOF-Jet prototype to his lab. That’s when he turned it over to graduate student Yalini Wijesundara, who had previously worked on jet injectors that shoot fluids. She posited that if Gassensmith’s injector could be modified to fire solids, then it would also be able to deliver cargo via MOFs, which are porous, crystalline structures that can hold almost anything.

The UT Dallas group had previously worked with the MOF ZIF-8, which is composed of zinc ion clusters linked by imidazolate ligands. It can be used to store vaccine formulations as powders at room temperature, unlike many liquid vaccines.

Of mice and onions

The team placed a variety of biological materials in ZIF-8, and then used their MOF-Jet to deliver the cargo into cells. They showed that their system was able to transport a ZIF-8-encased gene into onion cells and a protein into mice cells.

The group also discovered that the material’s release rate could be fine-tuned by changing the carrier gas in the injector. ZIF-8 is sensitive to acidic environments, which means that using carbon dioxide as the carrier gas leads to the MOF breaking down within 24 hours, whereas it’s still stable after 48 hours when using air.

The UT Dallas team is now testing its MOF-Jet to deliver chemotherapy agents to treat melanoma. Because it is able to disperse pharmaceuticals over a wide area, they hope the technology can distribute drugs more evenly in melanoma than a needle, which is the standard delivery method.

The preliminary results are promising. Gassensmith said his team will soon publish a paper showing that liposomes, which are particularly delicate, can be encapsulated in the MOF and shot through pig skin, which is very similar to human skin. ‘You can’t do that with a lot of biologicals, you can’t do that with liposomes at all,’ he says. ‘They just hit the skin and splatter … but if you put it in this coat of armour, you can put it in this gun and it will go right through any tissue, depending on how much pressure you want to apply.’ 

The MOF-Jet could also find use in veterinary medicine and agriculture. ‘The idea of being able to shoot genes into plants is really, really powerful because it doesn’t alter the germline, it doesn’t go into the seeds – it doesn’t make a permanent change,’ Gassensmith explained. ‘It just temporarily tells the plant to do something, like to hold off on fruiting if you know a frost is coming.’

Catherine Fromen, a chemical engineering professor at the University of Delaware whose work has evaluated the use of porous aluminum-based MOF nanoparticles as inhalable adjuvants, is enthusiastic about the work. Although she would like to see the full set of results from the UT Dallas team, Fromen says their concept is interesting and innovative. ‘The idea of putting MOFs, as drug delivery vaccine vehicles, in a dry powder has a lot of advantages, and then to be able to deliver them through this MOF-Jet, is really great,’ she says.

‘The ability to make things into a dry powder is really the holy grail of vaccine development and allowing things to be shelf-stable and not require any refrigeration,’ Fromen tells Chemistry World. However, she suggests that the details about which particular biologic is encapsulated in such a MOF are important.

Fromen says the MOF-Jet concept could have applications for large vaccination campaigns. ‘They used just ZIF-8, but you can imagine using a host of other types of MOFs, and the chemistry there matters – the size, shape, physical properties, chemical properties of the MOF will make a difference in how well the vaccine can be designed and how well it works,’ she states. ‘I think it’s an exciting area of research.’