A team of researchers has harnessed Google’s AI venture DeepMind to develop a bacterial injection system which can inject proteins, including cancer-killing drugs and gene therapies, directly into human cells.
Using the Artificial Intelligence (AI) tool AlphaFold the team including from the Massachusetts Institute of Technology (MIT) and Harvard University engineered a tiny syringe-like injection structure, naturally produced by Photorhabdus bacteria which primarily infects insects.
These syringe structures, described in the journal Nature, were used to deliver a range of useful proteins to both human cells and cells in live mice.
“Delivery of therapeutic molecules is a major bottleneck for medicine, and we will need a deep bench of options to get these powerful new therapies into the right cells in the body,” Feng Zhang Professor of Neuroscience at MIT.
“By learning from how nature transports proteins, we were able to develop a new platform that can help address this gap.”
Photorhabdus bacteria use the roughly 100-nanometre-long syringe-like machines to inject proteins into host cells to help adjust the biology of their surroundings and enhance their survival.
These machines, called extracellular contractile injection systems (eCISs), consist of a rigid tube inside a sheath that contracts, driving a spike on the end of the tube through the cell membrane.
This forces protein cargo inside the tube to enter the cell.
On the outside of one end of the eCIS are tail fibres that recognise specific receptors on the cell surface and latch on.
The researchers thought it might be possible to modify them to deliver proteins to human cells by re-engineering the tail fibres to bind to different receptors.
Using AlphaFold, which predicts a protein’s structure from its amino acid sequence, the researchers redesigned tail fibres of an eCIS produced by Photorhabdus bacteria to bind to human cells.
By re-engineering another part of the complex, the scientists tricked the syringe into delivering a protein of their choosing, in some cases with remarkably high efficiency.
The team made eCISs that targeted cancer cells expressing the EGF receptor and showed that they killed almost 100 per cent of the cells, but did not affect cells without the receptor.
Though efficiency depends in part on the receptor the system is designed to target, the researchers said that the findings demonstrate the promise of the system with thoughtful engineering.
The researchers also used an eCIS to deliver proteins to the brain in live mice — where it did not provoke a detectable immune response, suggesting that eCISs could one day be used to safely deliver gene therapies to humans.
