Scientists have refashioned a bacterium’s syringe, which is considered deadly to insect cells, into a nano injector that could potentially help develop critical tools for gene editing. The bacterium, called Photorhabdus asymbiotica, resides inside a caterpillar and possesses a contractile injection system called a syringe which releases toxic payload into insect cells. Researchers have now re-engineered this syringe to attach to human cells and inject large proteins that can edit the cell’s DNA.
Bacterial “Syrigine” Revolutionizing Protein Delivery in Biomedical Treatments
Traditional syringes have limitations when it comes to delivering precise inoculation. However, researchers at MIT have modified the Photorhabdus virulence cassette (PVC) protein to develop the syringe, commonly referred to as a “syrigine.” These PVCs are versatile and efficient delivery tools for various biomedical treatments. The AlphaFold AI program was used to predict suitable protein structures that could be re-engineered for injecting proteins into human cells.
The modified PVCs were customized for delivering specific cargo or treatment and can target human and mice cells with efficiencies approaching 100 percent. These bacterial syringes could potentially deliver treatments directly into human cells, including nanoscale carriers delivering antibodies into tumor cells. From biocontrol to human gene therapy, PVCs can be used in various applications.
Bacterial “Nanosyringes” Offer Possibility of Safer and More Effective Treatments
Proteins have more specific and powerful effects than small molecules but are unable to cross cell membranes, greatly limiting their uses. However, bacteria produce nanosyringes that bind to cells and forcibly inject their contents into them, which could be adapted to target human cells for protein delivery.
Researchers at MIT have successfully adapted Photorhabdus nanosyringes to target human cells and deliver different kinds of proteins to cells. The modified nanosyringe can hold around 10 proteins depending on size and is able to target specific cells such as those with the EGFR protein. The targeting specificity of the nanosyringe is exquisite and shows promise for treating various cancers and other conditions.
In a recent study, a modified nanosyringe was able to deliver proteins to neurons when injected into the brains of mice. While more work needs to be done to determine whether this technology could be useful in treating illness, especially in humans, these bacterial nanosyringes have opened up new possibilities for protein delivery.
Mass Production of Miniature Injectors Using Genetic Blueprints
The researchers mass-produced miniature injectors by inserting genetic blueprints for the injectors into Escherichia coli bacteria. They homed in on tentacle-like structures on the injectors called tail fibers, which grab and hold onto cells before the injector pierces cell membranes. Using AlphaFold, an artificial intelligence software, they engineered these tiny syringes to bind to mouse cells and injected them into the brain of a mouse, where they inserted a protein that made neurons glow.
Even though these injection systems consist of bacterial proteins, they could still lead to immune reactions in humans. Down the road, it will be important to test the technology in higher mammals. However, researchers are optimistic about the potential of this technology for delivering precise treatments.
Nano Injector Offers Promise for Cancer Treatment
The syringe technology also holds promise for treating cancer because it can be engineered to attach to receptors on some human cancer cells. Bacteria have been modified so that their nano injectors can deliver therapeutic proteins that activate or inhibit genes that lead cancer cells to commit suicide; block co-opted signaling pathways and starve the tumor by preventing angiogenesis, the growth of new blood vessels; and enhance the immune response to prevent the spread of cancer.
In summary, researchers have developed a bioluminescent bacterial syringe that has overcome one of the biggest unsolved problems for gene editing: delivering genetic material and proteins into cells precisely. From biocontrol tools to human gene therapy, bacterial syringes could be used for various applications in protein delivery to treat diseases. The development of these bacterial syringes is a major breakthrough and presents immense possibilities for future scientific research.
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