Radically different
Nature Medicine, Published online: 29 April 2026; doi:10.1038/s41591-026-04338-1
A multicountry cohort study found that prediction models combining clinical parameters with either pulse oximetry or the host biomarker sTREM1 more accurately identified febrile children needing referral than standard WHO criteria.
Nature Medicine, Published online: 29 April 2026; doi:10.1038/s41591-026-04366-x
Preclinical and phase 1/2 trial data show that anti-CD38 monoclonal antibody treatment restores platelet counts in patients with immune thrombocytopenia by increasing nicotinamide adenine dinucleotide (NAD+) levels, and low-dose oral treatment with the NAD+ precursor nicotinamide mononucleotide can similarly increase platelet counts without serious adverse effects.
Nature Medicine, Published online: 29 April 2026; doi:10.1038/s41591-026-04357-y
Evaluated across 18 multicancer cohorts, the agentic artificial intelligence workflow SPARK uses language as a universal interface to autonomously generate biological ideas.
Nature Neuroscience, Published online: 29 April 2026; doi:10.1038/s41593-026-02280-6
How the brain organizes the retrieval of old and new memories remains unknown. Kim et al. identify a septo−entorhinal GABAergic pathway that controls flexible switching between episodic memories during memory retrieval to enable memory updating.
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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.