Photorhabdus bacterium nanosyringe seen under an electron microscope
Joseph Kreitz, Massachusetts Institute of Technology and Harvard Broad Institute, Massachusetts Institute of Technology McGovern Brain Institute
Thanks to bacterial ‘nanosyringes’ fine-tuned to target human cells, it may be possible to inject proteins into specific cells in the body. This may enable safer and more effective treatments for various diseases, including cancer.
When the pill is swallowed, the small molecules inside diffuse from the blood into the cells. However, because small molecules can easily enter cells, they are often less specific and have unwanted side effects.
Large molecules such as proteins have much more specific and potent effects than small molecule drugs. However, their inability to cross the cell membrane to enter the cell severely limits their use. Effective ways to get proteins into cells in the body could open the door to innovative treatments for a variety of conditions.
Many groups around the world are trying to solve this delivery problem, but progress has been limited so far. Joseph Kreitz of the Massachusetts Institute of Technology (MIT) said:
But bacteria have already solved this problem. Many produce cylindrical structures that bind to cells and force their contents into the cells. “They are very similar to syringes,” he says Kreitz.
These nanosyringes resemble phage viruses that infect bacteria, presumably as a result of bacteria taking up viruses and turning them into weapons.
especially, photolabdas When bacteria infect insects, they release nanosyringes containing toxic proteins. Nanosyringes bind to specific proteins in insect cells and inject toxins into these cells, killing them so that bacteria can eat them.
Kreitz and his colleagues photolabdas Nanosyringes targeting human cells. They first used the AlphaFold AI program to predict the structure of the nanosyringe, including the portion that binds to protein receptors on the outside of the cell and triggers injection.
This section was then tweaked to bind to a human protein called EGFR on the outside of some cells, and AlphaFold was used again to examine the effect of tweaking. The team showed that this modified nanosyringe could deliver several different types of proteins of varying sizes into human cells bearing the EGFR protein.
“The fact that this can load different payloads of different sizes is unique among protein delivery devices,” says Kreitz. Each nanosyringe can hold about 10 proteins, depending on size, he says.
Injecting the toxin into the nanosyringe killed the cells with the EGFR protein, but left other cells intact.
MIT team leader Feng Zhang said: “It’s very exciting.”
This indicates that the nanosyringe can be programmed to target any type of cell, potentially including various cancers.
The researchers also showed that another nanosyringe, fine-tuned to target mouse cell-surface proteins, could deliver proteins to neurons when injected into the mouse brain. Importantly, however, we have not yet shown that nanosyringes can deliver proteins to cells after being injected into the bloodstream.
Amin Hajitou of Imperial College London says he modified a phage virus to target human cancer cells. But the team needs to do more work to show that it could help treat the disease, he says.
Even if nanosyringes worked when injected into the blood, they could still be considered foreign and trigger the production of antibodies. Yes, meaning these treatments cannot be repeated over time. This is a big limitation.
But Kreitz says he has already “decorated” the barrel of the nanosyringe by adding small proteins. In this way, he says, the nanosyringes could be hidden from the immune system.
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