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As people age, their immune function weakens. Owing to shrinkage of the thymus, where T cells normally mature and diversify, populations of these immune cells become smaller and can’t react to pathogens as quickly. But researchers at MIT and the Broad Institute have now found a way to overcome that decline by temporarily programming cells in the liver to improve T-cell function. 

To create a “factory” for the T-cell-stimulating signals that are normally produced by the thymus, the researchers identified three key factors that usually promote T cells’ maturation and encoded them into mRNA sequences that could be delivered by lipid nanoparticles. When injected into the bloodstream, these particles accumulate in the liver and the mRNA is taken up by the organ’s main cells, hepatocytes, which begin to manufacture the proteins encoded by the mRNA. 

Aged mice that received the treatment showed much larger and more diverse T-cell populations in response to vaccination, and they also responded better to cancer immunotherapy treatments.

If this type of treatment is developed for human use, says Professor Feng Zhang, the senior author of a paper on the work, “hopefully we can help people stay free of disease for a longer span of their life.” 

Researchers at MIT and Microsoft have used artificial intelligence to create molecular sensors that could detect early signs of cancer via a urine test.

The researchers developed an AI model to design short proteins that are targeted by enzymes called proteases, which are overactive in cancer cells. Nanoparticles coated with these proteins, called peptides, can give off a signal if they encounter cancer-­linked proteases once introduced into circulation: The proteases will snip off the peptides, which then form reporter molecules that are excreted in urine.

Sangeeta Bhatia, SM ’93, PhD ’97, a senior author of a paper on the work with her former student Ava Amini ’16, a principal researcher at Microsoft Research, led the MIT team that came up with the idea of such particles over a decade ago. But earlier efforts used trial and error to identify peptides that would be cleaved by specific proteases, and the results could be ambiguous. With AI, peptides can be designed to meet specific criteria.

“If we know that a particular protease is really key to a certain cancer, and we can optimize the sensor to be highly sensitive and specific to that protease, then that gives us a great diagnostic signal,” Amini says. 

Bhatia’s lab is now working with ARPA-H on an at-home kit that could potentially detect 30 types of early cancer. Peptides designed using the model could also be incorporated into cancer therapeutics.

Antibody treatments for cancer and other diseases are typically delivered intravenously, requiring patients to go to a hospital and potentially spend hours receiving infusions. Now Professor Patrick Doyle and his colleagues have taken a major step toward reformulating antibodies so that they can be injected with a standard syringe, making treatment easier and more accessible. 

The obstacle to injecting these drugs is that they are formulated at low concentrations, so very large volumes are needed per dose. Decreasing the volume to the capacity of a standard syringe would mean increasing the concentration so much that the solution would be too thick to be injected.

In 2023, Doyle’s lab developed a way to generated highly concentrated antibody formulations by encapsulating them into hydrogel particles. However, that requires centrifugation, a step that would be difficult to scale up for manufacturing.

In their new study, the researchers took a different approach that instead uses a microfluidic setup. Droplets containing antibodies dissolved in a watery prepolymer solution are suspended in an organic solvent and can then be dehydrated, leaving behind highly concentrated solid antibodies within a hydrogel matrix. Finally, the solvent is removed and replaced with an aqueous solution.

Using semi-solid particles 100 microns in diameter, the team showed that the force needed to push the plunger of a syringe containing the solution was less than 20 newtons. “That is less than half of the maximum acceptable force that people usually try to aim for,” says Talia Zheng, an MIT graduate student who is the lead author of the new study.

More than 700 milligrams of the antibody—enough for most therapeutic applications—could be administered at once with a two-milliliter syringe. The formulations remained stable under refrigeration for at least four months. The researchers now plan to test the particles in animals and work on scaling up the manufacturing process.