New Delhi: A team of researchers has used Google’s AI venture DeepMind to develop a bacterial injection system that can inject cancer-killing drugs and proteins including gene therapy directly into human cells. The team, including those from the Massachusetts Institute of Technology (MIT) and Harvard University, used the artificial intelligence (AI) tool AlphaFold to build a tiny syringe-like injection structure naturally produced by Photorhabdous bacteria that primarily infect insects. does.
These syringe structures, described in the journal Nature, were used to deliver useful proteins to both human cells and cells in living mice. “Delivery of therapeutic molecules is a major hurdle for medicine, and we will need a deep bench of options to get these powerful new therapies into the right cells in the body,” said Feng Zhang Professor of Neuroscience at MIT. “
“By learning from how nature transports proteins, we were able to develop a new platform that may help bridge this gap.” Photorhabdus bacteria use approximately 100-nanometer-long syringe-like machines to inject proteins into host cells to help them adjust to their surrounding biology and enhance their survival. These machines, called extracellular contractile injection systems (eCIS), consist of a rigid tube inside a sheath, which drives a spike at the end of the tube through the cell membrane. This forces the protein cargo inside the tube to enter the cell. Out of one end of the ECIS are tail filaments that recognize and move through specific receptors on the cell surface.
The researchers thought it might be possible to modify the tail fibers to deliver proteins to human cells by re-engineering them to bind different receptors. Using AlphaFold, which predicts the structure of a protein from its amino acid sequence, the researchers redesigned the tail fibers of an eCIS produced by Photorhabdus bacteria to bind to human cells. By re-engineering the other part of the complex, the scientists tricked the syringe into delivering the protein of their choosing, in some cases with remarkably high efficiency. The team created ECIs targeting cancer cells that expressed the EGF receptor and showed that they killed nearly 100 percent of the cells, but did not affect cells without the receptor.
Although efficiency depends partly on the receptor the system is designed to target, the researchers said the findings demonstrate the promise of systems with thoughtful engineering. The researchers also used an ECIS to deliver the protein to the brain in live mice – where it did not provoke a detectable immune response, suggesting that ECIS could one day be used to safely deliver gene therapy to humans. Can be used.