New Programmable System Developed to Deliver Protein Treatments into Human Cells and Animals
Scientists are working on a programmable system that can eventually be used in medical treatments like gene therapy and cancer therapy.
Scientists from the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT recently invented a new type of protein delivery method. It will work with both human cells and animals, and can be programed to bring different types of proteins into a cell, including ones used in gene editing and cancer treatments. In other words, this system may offer a safe and effective way to deliver therapies through gene therapy or to cure cancer in the future.
Feng Zhang, a researcher from the Broad Institute and McGovern Institute, used an injection system made by bacteria to deliver proteins into human cells and live mice. The injection system was improved with help from artificial intelligence tool AlphaFold, allowing it to work effectively on both human cells and live mice.
Joseph Kreitz, the person who wrote this study and a student in Zhan’s lab said that this is very cool because it shows how changing proteins can affect natural things. He thinks protein engineering is helpful for creating new medicines to help people!
Researchers at MIT and Howard Hughes Medical Institute have developed a new platform to help overcome the problem of getting useful treatments into people’s bodies. This platform was based on observing how nature moves proteins around. The study was led by James and Patricia Poitras Professor of Neuroscience Zhang from MIT.
“Tiny Machines To Battle Cancers
Certain bacteria live in close relationships (symbiotic) with other organisms and use special machines to help them survive. These machines are called extracellular contractile injection systems, or eCISs. They look like tiny syringes, measuring only 100 nanometers in length – that’s really small! The eCISs have a spike on one end that punctures the cell wall of its host. This spike pushes protein cargo into the cell, allowing bacteria to alter their environment and increase their survival rate.
At one end of the eCIS there are special strings that can attach to specific spots on cell surfaces. Scientists already know the eCISs can find and target insect and mouse cells, but it may be possible to reprogram these tails so that they bind with human cells instead and deliver proteins to them.
Researchers used a tool called AlphaFold to change the tail fibers of bacteria-made eCIS so that it can bind with human cells. Also, by altering another part of the structure, scientists achieved successful outcomes in delivering their desired proteins in high amounts to the humans.
The scientists invented special chemicals (eCISs) that only affected cancer cells with EGF receptors. Almost all of the targeted cells were killed and none of the other cells in their experiment were hurt, proving how powerful they are. Depending on which receptor they use, the strength of this system varies, but it is still a very effective way to battle cancers.
Scientists tested an eCIS and found that it could deliver proteins to the brains of live mice without causing any problems. This means that eCISs might be used to safely inject gene therapies into humans someday.
Unlocking Nature’s Programmable Protein Delivery System
Kreitz has explained that the eCIS system is really useful and can be used to deliver different things. These include proteins which can change a single letter in DNA, proteins which are dangerous for cancer cells, as well as Cas9 – an enzyme that cuts up DNA and is used in many gene-editing processes.
In the future, researchers could modify the eCIS system to do things like change specific properties and transport other materials such as DNA or RNA. Scientist have seen that this system is used a lot in nature, but still don’t know why exactly – so they want to learn more about what role it plays.
Scientists figured out how bacteria can be used to deliver proteins into our bodies. This process was recently published in an article called “Programmable Protein Delivery with a Bacterial Contractile Injection System,” written by Joseph Kreitz, Mirco J. Friedrich, Akash Guru, Blake Lash, Makoto Saito, Rhiannon K. Macrae and Feng Zhang and published in the journal Nature on March 29th, 2023.
This work was partly funded by some important organizations, which includes the National Institutes of Health, Howard Hughes Medical Institute, and several Centers for Research at MIT. It was also supported financially through generous donations from a few people such as W. Ackman, N. Oxman, J. and P. Poitras, BT Charitable Foundation, C. and L Asness, the Phillips family, D Cheng and R Metcalfe.
