Google AI-powered tiny syringe to deliver gene therapy and cancer-killing drugs

 These syringe structures, described in Nature, were used to deliver a variety of useful proteins to human cells as well as cells in living mice.

A team of researchers has used Google's AI venture DeepMind to create a bacterial injection system that can inject proteins directly into human cells, including cancer-killing drugs and gene therapies.

Using the Artificial Intelligence (AI) tool AlphaFold, the team from MIT and Harvard University engineered a tiny syringe-like injection structure that is naturally produced by Photorhabdus bacteria, which primarily infects insects.

These syringe structures, described in Nature, were used to deliver a variety of useful proteins to human cells as well as cells in living mice.

"Delivery of therapeutic molecules is a major bottleneck for medicine," says Feng Zhang, Professor of Neuroscience at MIT.

"We were able to develop a new platform that can help address this gap by learning from how nature transports proteins."

Photorhabdus bacteria use the 100-nanometer-long syringe-like machines to inject proteins into host cells in order to alter the biology of their surroundings and increase their chances of survival.

Extracellular contractile injection systems (eCISs) are machines that 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 the protein cargo contained within the tube to enter the cell.

Tail fibres on the outside of one end of the eCIS recognise and latch on to specific receptors on the cell surface.

The researchers reasoned that by re-engineering the tail fibres to bind to different receptors, they might be able to modify them to deliver proteins to human cells.

The researchers redesigned the tail fibres of an eCIS produced by Photorhabdus bacteria to bind to human cells using AlphaFold, a programme that predicts the structure of a protein based on its amino acid sequence.

The scientists tricked the syringe into delivering a protein of their choice by re-engineering another part of the complex, in some cases with remarkably high efficiency.

The researchers created eCISs that targeted cancer cells expressing the EGF receptor and demonstrated that they killed nearly 100% of the cells but had no effect on cells lacking the receptor.

Though efficiency is dependent in part on the receptor the system is designed to target, the researchers stated that the findings show the system's promise with careful engineering.

The researchers also used an eCIS to deliver proteins to the brain of live mice, where there was no detectable immune response, implying that eCISs could be used to safely deliver gene therapies to humans in the future.