Monday, June 24, 2024

Artificial Intelligence news

Synthesia’s hyperrealistic deepfakes will...

Startup Synthesia’s AI-generated avatars are getting an update to make them even...

How underwater drones could...

A potential future conflict between Taiwan and China would be shaped by...

How generative AI could...

First, a confession. I only got into playing video games a little...

I tested out a...

This story first appeared in China Report, MIT Technology Review’s newsletter about...
HomeArtificial IntelligenceBacterial injection system...

Bacterial injection system delivers proteins in mice and human cells



Researchers at the McGovern Institute for Brain Research at MIT and the Broad Institute of MIT and Harvard have harnessed a natural bacterial system to develop a new protein delivery approach that works in human cells and animals. The technology, described today in Nature, can be programmed to deliver a variety of proteins, including ones for gene editing, to different cell types. The system could potentially be a safe and efficient way to deliver gene therapies and cancer therapies.

Led by MIT Associate Professor Feng Zhang, who is a McGovern Institute investigator and Broad Institute core member, the team took advantage of a tiny syringe-like injection structure, produced by a bacterium, that naturally binds to insect cells and injects a protein payload into them. The researchers used the artificial intelligence tool AlphaFold to engineer these syringe structures to deliver a range of useful proteins to both human cells and cells in live mice.

“This is a really beautiful example of how protein engineering can alter the biological activity of a natural system,” says Joseph Kreitz, the study’s first author, a graduate student in biological engineering at MIT, and a member of Zhang’s lab. “I think it substantiates protein engineering as a useful tool in bioengineering and the development of new therapeutic systems.”

“Delivery of therapeutic molecules is a major bottleneck for medicine, and we will need a deep bench of options to get these powerful new therapies into the right cells in the body,” adds Zhang. “By learning from how nature transports proteins, we were able to develop a new platform that can help address this gap.”

Zhang is senior author on the study and is also the James and Patricia Poitras Professor of Neuroscience at MIT and an investigator at the Howard Hughes Medical Institute.

Injection via contraction

Symbiotic bacteria use the roughly 100-nanometer-long syringe-like machines to inject proteins into host cells to help adjust the biology of their surroundings and enhance their survival. These machines, called extracellular contractile injection systems (eCISs), 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 protein cargo inside the tube to enter the cell.

On the outside of one end of the eCIS are tail fibers that recognize specific receptors on the cell surface and latch on. Previous research has shown that eCISs can naturally target insect and mouse cells, but Kreitz thought it might be possible to modify them to deliver proteins to human cells by re-engineering the tail fibers to bind to different receptors.

Using AlphaFold, which predicts a protein’s structure from its amino acid sequence, the researchers redesigned tail fibers of an eCIS produced by Photorhabdus bacteria to bind to human cells. By re-engineering another part of the complex, the scientists tricked the syringe into delivering a protein of their choosing, in some cases with remarkably high efficiency.

The team made eCISs that targeted cancer cells expressing the EGF receptor and showed that they killed almost 100 percent of the cells, but did not affect cells without the receptor. Though efficiency depends in part on the receptor the system is designed to target, Kreitz says that the findings demonstrate the promise of the system with thoughtful engineering.

The researchers also used an eCIS to deliver proteins to the brain in live mice — where it didn’t provoke a detectable immune response, suggesting that eCISs could one day be used to safely deliver gene therapies to humans.

Packaging proteins

Kreitz says the eCIS system is versatile, and the team has already used it to deliver a range of cargoes including base editor proteins (which can make single-letter changes to DNA), proteins that are toxic to cancer cells, and Cas9, a large DNA-cutting enzyme used in many gene editing systems.

In the future, Kreitz says researchers could engineer other components of the eCIS system to tune other properties, or to deliver other cargoes such as DNA or RNA. He also wants to better understand the function of these systems in nature.

“We and others have shown that this type of system is incredibly diverse across the biosphere, but they are not very well characterized,” Kreitz said. “And we believe this type of system plays really important roles in biology that are yet to be explored.”

This work was supported, in part, by the National Institutes of Health, Howard Hughes Medical Institute, Poitras Center for Psychiatric Disorders Research at MIT, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, K. Lisa Yang and Hock E. Tan Molecular Therapeutics Center at MIT, K. Lisa Yang Brain-Body Center at MIT, Broad Institute Programmable Therapeutics Gift Donors, The Pershing Square Foundation, William Ackman, Neri Oxman, J. and P. Poitras, Kenneth C. Griffin, BT Charitable Foundation, the Asness Family Foundation, the Phillips family, D. Cheng, and R. Metcalfe.



Article Source link and Credit

Continue reading

Understanding the visual knowledge of language models

You’ve likely heard that a picture is worth a thousand words, but can a large language model (LLM) get the picture if it’s never seen images before?As it turns out, language models that are trained purely on text...

A smarter way to streamline drug discovery

The use of AI to streamline drug discovery is exploding. Researchers are deploying machine-learning models to help them identify molecules, among billions of options, that might have the properties they are seeking to develop new medicines.But there are...

Technique improves the reasoning capabilities of large language models

Large language models like those that power ChatGPT have shown impressive performance on tasks like drafting legal briefs, analyzing the sentiment of customer reviews, or translating documents into different languages.These machine-learning models typically use only natural language to...