Radically different
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Morning. In the same way that Athena orchestrated the logistics around Telemachus’s journey in the first three books of “The Odyssey,” I hope some gods out there are coordinating a “Survivor” season 50 win for Cirie Fields. She’s earning it, but I wouldn’t mind some divine intervention to make sure.
mRNA vaccines work by delivering genetic instructions into cells, but a new study shows that which cells express the mRNA can alter the resulting immune response. A new study in Nature Biotechnology shows that detargeting mRNA expression away from hepatocytes strengthens T‑cell immunity in preclinical lymphoma models, revealing a new design principle for next‑generation mRNA vaccines and therapeutics.
The work comes from researchers at the Icahn School of Medicine at Mount Sinai, who report that non‑immune cells—including muscle fibers and hepatocytes—play a decisive role in determining mRNA vaccine potency. Their paper, “mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression,” was published today. The findings overturn a long‑held assumption that mRNA vaccines must deliver their payload to dendritic cells to prime strong T‑cell responses.
“This study fundamentally changes how we think mRNA vaccines work,” said senior author Brian D. Brown, PhD, director of the Icahn Genomics Institute. “For years, the field has assumed that getting the mRNA into dendritic cells, the immune cells that activate T cells, was essential. We show that’s not the case. These cells are still important, but mRNA delivery to them is not required.”
To dissect how different cell types influence immunity, the team used a microRNA‑based technology developed in Brown’s lab that allows researchers to “turn off” mRNA expression in specific cell populations. By incorporating short microRNA target sequences into the mRNA, they selectively silenced expression in dendritic cells, hepatocytes, or muscle cells while leaving other tissues unaffected.
The results were striking. Silencing mRNA expression in dendritic cells did not impair T‑cell priming, including for SARS‑CoV‑2 antigens, suggesting that cross‑presentation by other cell types is sufficient to initiate immunity. “This was unexpected,” said Brown. “It tells us that other cells are producing the vaccine antigen and handing it off to the immune system.” In contrast, turning off expression in muscle fibers weakened the immune response, while turning off expression in hepatocytes tripled it.
“We found that hepatocytes actively dampen the immune response to mRNA vaccines,” said Sophia Siu, an MD/PhD student and co‑lead author. “This is notable because hepatocytes can take up a lot of mRNA, particularly when it’s injected intravenously. For vaccines, we discovered that we don’t want expression in hepatocytes. However, for mRNA therapeutics, hepatocyte expression can be beneficial because it may help prevent immunity to the mRNA-encoded protein.”
“In mice bearing tumor-associated antigen (TAA)-expressing lymphoma cells, miRT-mediated hepatocyte-silenced TAA mRNA vaccine enhanced immune response and reduced tumor burden,” wrote the authors. The approach also reduced hepatocyte death when mRNA was used to boost pre‑existing T cells, an important consideration for gene‑editing and CAR T–related applications.
“These results show that we can make mRNA cancer vaccines more effective simply by controlling where the mRNA‑encoded antigen is expressed,” said Joshua D. Brody, MD, director of the Lymphoma Immunotherapy Program at the Mount Sinai Tisch Cancer Center. “It’s a new lever for improving immunotherapy.”
Beyond oncology, the findings could influence the design of mRNA‑based vaccines for infectious diseases and therapeutics for autoimmune and genetic disorders. By tuning expression in specific cell types, researchers can amplify or dampen immune responses as needed.
“mRNA technology is transformative for medicine,” Brown said. “Our work provides a new set of design rules for mRNA vaccines and therapeutics. As this technology continues to evolve, understanding and controlling where mRNA is expressed will be critical.”
The post Hepatocyte Detargeting Improves mRNA Vaccine Immunity in Lymphoma Model appeared first on GEN – Genetic Engineering and Biotechnology News.
If all goes well — which is to say if you are generally healthy — you mostly experience the doctor’s office as an inconvenience, going to primary care appointments that are an hour of waiting for 20 minutes of care.
If you’re ill, you fall into a Kafka-esque labyrinth of specialists, waiting rooms, and prior authorizations. You will be held tightly by the medical system, but you are unlikely to feel good.
One of health secretary Robert F. Kennedy’s refrains has focused on medical education: Doctors don’t know enough about nutrition and preventive medicine, he likes to say. He has encouraged medical schools to beef up (tallow up?) their education on healthy eating and its connection to chronic disease.
What do medical students think of this?
I’ve been waiting for health secretary Robert F. Kennedy Jr. to do something big on oversight of what I call pop peptides, like BPC-157 and GHK-Cu. He had long signaled that he was going to free such peptides from what he saw as a past, misguided FDA that had banned them in 2023.
It’s finally happened — and the way it went down shook me up a bit.
For a few years, a loophole in compounding rules had allowed specialty pharmacies to make and market these peptides. It effectively meant that substances nominated for compounding — even unproven drugs — could be made and marketed by qualified pharmacies while the FDA pondered the nominations. But in 2023, the Food and Drug Administration rightly moved peptides to a no-compounding-allowed status called Category 2 due to concerns about safety and lack of clinical trial data. Now Kennedy is working to undo that with major risks to the public.
Today, nuclear energy enjoys a rare moment of support across the political spectrum in the US. Interest from tech companies that are scrambling to meet demand for massive data centers has sparked a resurgence of money and attention in the industry. That newfound interest is exactly why it’s time to talk about an old problem: nuclear waste.
In the US alone, nuclear reactors produce about 2,000 metric tons of high-level waste each year. And there’s nowhere to put it.
Though newly popular, the nuclear program in the US is nothing new. The US hosts more reactors and production capacity than any other country in the world. And yet nearly seven decades after the first permanent nuclear facility in the US went online, there’s still not a long-term solution for nuclear waste.
Used fuel is largely stored onsite at operating and shut-down reactors, in pools and casks made of steel and concrete. Experts generally agree that these methods are safe, but they’re not designed to be permanent.
The leading strategy around the world for long-term storage of this high-level radioactive waste is to house it in a deep geological repository—dig a hole, put radioactive material down there, and fill it up with concrete. These holes, hundreds of meters underground, are designed to be a permanent home.
There aren’t any operating geological repositories for spent fuel yet, but some countries are well on their way. Finland is the furthest along; as of 2026, the country is testing its facility. Final approvals are expected soon, and operations could start later this year. Some other countries aren’t far behind.
France is home to over 50 nuclear reactors, and its grid gets more of its power from nuclear than any other. The country also has the world’s most established program for reprocessing spent fuel. The process separates out the plutonium and uranium to create a type of fuel known as mixed oxide (MOX) fuel. But reprocessing isn’t a perfect recycling loop, so the leftovers from this process still need somewhere to go. The country currently stores waste onsite at the La Hague reprocessing plant, but it plans to build a repository. Initial approvals could come later this decade, and pilot operations could start up by 2035.
Technically, the US also has a destination for its spent fuel: Yucca Mountain in Nevada. The site, which is on federal land, was designated by Congress in 1987. However, progress has entirely stalled out because of political opposition. In 2011, the federal government stopped providing funding for the site, and for roughly a decade, there’s been no activity to speak of.
In the meantime, waste continues to pile up.
The nuclear industry is kicking into a new gear around the world. China is home to the world’s fastest–growing nuclear energy program, and countries including Bangladesh and Turkey are building their first reactors.
Even the long-established US program is seeing growth: Interest in and approval for nuclear energy have spiked, and Big Tech is throwing money around to meet rising electricity demand. Companies are proposing (and beginning to receive regulatory approval for) next-generation reactors, which employ different coolants, fuels, and designs.
Given all this new interest, and the impending arrival of new types of nuclear waste, it’s time for nuclear companies, as well as their powerful customers, to push for progress on building geological storage facilities. As the richest country on the planet and home to a large chunk of the activity in next-generation reactors, the US should aim to join the leaders rather than continue to lag behind.
Directing even a small fraction of the recent surge in funding and attention to progress on waste could make a difference. Some experts are calling for a new organization in the US to manage nuclear waste rather than leaving it to the Department of Energy. This organization would mirror programs in Finland, Canada, and France.
The process of planning, building, and commissioning a permanent solution for nuclear waste is a long one. Finland started planning in the 1980s and selected its site in the early 2000s, and it’s nearly ready to start accepting waste. For countries that don’t have a permanent storage solution sorted, the best time to start was decades ago. But the second-best time is now.
This article is from The Spark, MIT Technology Review’s weekly climate newsletter. To receive it in your inbox every Wednesday, sign up here.
A report released Wednesday highlights successes in reducing health disparities in U.S. states. Since the last iteration of the analysis by the Commonwealth Fund, two states expanded eligibility for Medicaid, many states extended postpartum coverage for mothers, and enrollment in Affordable Care Act marketplace plans increased at an unprecedented clip.
But given the report covered the years 2022 to 2024, many equity researchers fear the gains may be short-lived. Outside experts who reviewed the report predict that policies from the second Trump administration, including changes to insurance coverage and vaccine policies and cuts to programs promoting diversity, equity, and inclusion, will exacerbate inequities.