James Dahlman and Phil Santangelo are helping to define an evolving era in medicine, one in which messenger ribonucleic acid—mRNA—can be delivered directly to cells to fight against disease. And their latest groundbreaking study could clear the way to faster therapeutic discoveries.
“Our work is very compatible,” said Dahlman, associate professor and McCamish Foundation Early Career Professor. “Phil’s lab designs and manufactures really high-quality mRNA, and my lab develops the lipid nanoparticles to deliver it.”
Therapeutics made from mRNA or DNA hold promise in addressing lots of diseases, explained Santangelo, a professor in Coulter BME, “but they’re not much good if they can’t get where they need to go. If you make cargo, which is essentially what we do in my lab, you need delivery, so James and I have a very natural collaboration.”
Their partnership, which began when Dahlman arrived at Georgia Tech in 2016, consistently yields results published in high-impact journals and garners generous research grants from federal agencies, including the National Institutes of Health (NIH) and the Defense Advanced Research Projects Agency (DARPA).
That includes a recent flood of cutting-edge papers: two in Nature Biomedical Engineering (from October 2021, and a forthcoming study) as well as their latest publication, released Feb. 7 in Nature Nanotechnology.
“We’re reporting an improved barcoding system that would make animal pre-clinical nanoparticle studies more predictive, speeding up the development of RNA therapies,” Dahlman said.
Several years ago, Dahlman and collaborators developed a technique called “DNA barcoding,” which allows for the rapid, simultaneous screening of many of his custom-made delivery vehicles—what are called lipid nanoparticles, or LNPs. Scientists insert unique snippets of DNA into different LNPs, which are injected into mice. Genetic sequencing is then used to determine which barcodes have reached which specific targets.
The new system described in Nature Nanotechnology takes the screening process a step further.
“Lipid nanoparticles are usually developed in mice, but when you move them into another species, like a non-human primate—because that’s the natural progression, a primate is more like a human—they frequently don’t work as well,” Santangelo said. “When they don’t, you have to go back and make adjustments.”
But what if you could streamline the process?
The genes that affect LNP delivery vary between pre-clinical species and humans, though the extent of those differences is unknown because studies comparing nanoparticle delivery across species have been very difficult to perform. Until now. To speed that process, the researchers developed a new testing system they’re calling Species Agnostic Nanoparticle Delivery Screening, or SANDS.
Using SANDS, the team compared nanoparticle delivery simultaneously in mouse, primate, and living human cells, all within specially engineered mice.
“We can actually put the same group of nanoparticles in all three and compare delivery across species,” Dahlman said. “We found what you might expect: delivery in the primate cells predicted really well how delivery in the human cells would go, whereas the mouse cells were less predictive.”
Unlike the previous barcoding system, which worked well in mouse cells, SANDS needed a different kind of marker for screening, a molecule called reporter mRNA. Santangelo’s lab developed one, “and it basically gets around the limitations of the old system,” he said. “Now we can screen new lipid nanoparticles in mice with primate and human cells.”
SANDS already is facilitating further studies for the research team.
Going forward, Dahlman and Santangelo believe that deeper understanding of the different mechanisms driving delivery in mouse cells and other cells will result in a more efficient selection process for LNPs, making pre-clinical nanoparticle studies more predictive and accelerating the development of RNA therapies.
That sense of building momentum has been kind of a theme for the Dahlman-Santangelo partnership since it began. Dahlman remembered interviewing at Georgia Tech and Emory and being immediately impressed when he met Santangelo.
“I explained to him my vision for barcoding, and he immediately got it; he explained to me his vision for improving payloads, and I immediately got that,” Dahlman said. “You could have the world’s best nanoparticle, but if you don’t put optimized mRNA in it, that’s not going to be any good.”
They immediately recognized the value and the necessity for collaboration, especially because, as Santangelo put it, “This is a wildly competitive time in mRNA research.”
The pace of their work reflects that, too. Their October study in Nature Biomedical Engineering reported development of an LNP designed specifically to be delivered by a nebulizer into the lungs. In their experiments, it successfully delivered therapeutic mRNA and protected mice from a lethal flu. They’ve got several more papers nearing publication.
And there’s work soon to be funded by the Wellcome Leap program that includes a project focused on mRNA-encoded antibodies for the lung. They’re also developing what could be another game-changer in vaccinations—what Santangelo described as “a new type of approach that has a lot of potential: The basic idea is to have the ability to vaccinate against many pathogens at once.”
Ultimately, though, it comes back to having the best vehicle to deliver the potent payload; you can’t really have one without the other. The Dahlman-Santangelo research partnership is complementary in other ways as well, with Dahlman’s lab doing a lot of the sequencing and Santangelo’s lab doing a lot of the imaging.
“It means that we can write papers that are much more complete,” Santangelo said. “It includes all of the data, and it can have sequencing, it can have imaging, it has fancy cargoes, it has cool delivery. You put together all of those pieces, and you have a nice package.”
News
Half of vaccines are binned – ‘fridge-free’ versions could change that
Vaccines that do not need to be kept cool in a fridge have been successfully trialed in patients for the first time, say UK scientists. Currently, most vaccines need to be refrigerated or frozen [...]
Mushroom Mystery: The Fungus That Makes People See Tiny Humans
A mushroom sold in markets and served in restaurants in Southwest China has an unusual warning attached to it: cook it thoroughly, or you may start seeing tiny people. For decades, people have reported [...]
Artificial intelligence used to design brand new viruses
Artificial Intelligence has been used to design brand new viruses that are fully functional and can replicate in the laboratory, say US researchers. It is the first time whole genomes have been successfully designed [...]
Molecular Manufacturing: The Future of Nanomedicine – New book from NanoappsMedical Inc.
This book explores the revolutionary potential of atomically precise manufacturing technologies to transform global healthcare, as well as practically every other sector across society. This forward-thinking volume examines how envisaged Factory@Home systems might enable the cost-effective [...]
Moderna kicks off Phase I Ebola trial as Africa readies itself for research
If the Phase I trial is successful, Moderna plans to quickly initiate Phase II and Phase III trials of its Ebola vaccine. Moderna has initiated a Phase I trial of its mRNA Ebola vaccine [...]
3D Human Brain Tissue Model Replicates Alzheimer’s Pathology
Summary: Researchers introduced a highly reproducible three-dimensional human brain tissue model capable of replicating complex neurodegenerative processes in Alzheimer’s disease. Developed over nine years using human stem cells, the self-organizing tissue spheroids integrate functional neurons, [...]
A Common Sugar May Loosen Cancer Cells and Help Them Spread
Chemotherapy may kill most ovarian cancer cells, but the few that survive can turn dangerously active. By releasing fructose, they may help nearby tumor cells break free and spread. Researchers at The Wistar Institute [...]
COVID-19 can wake up dormant viruses in the body, large study confirms
Virus reactivations by SARS-CoV-2 could worsen initial symptoms and increase risk of Long Covid. Early in the COVID-19 pandemic, scientists noticed that a SARS-CoV-2 infection can “wake up” other, dormant viruses already present in [...]
Scientists Discover the Brain May Enter a New Biological Phase Between 50 and 75
A single-cell study reveals major changes in immune cells, genome organization, and gene regulation within the aging human hippocampus, offering important insights into brain aging and dementias associated with age. Between roughly ages 50 [...]
Our books now available worldwide!
Online Sellers other than Amazon, Routledge, and IOPP Indigo Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artifcial Intelligence Global Health Care Equivalency In The Age Of Nanotechnology, Nanomedicine And Artificial [...]
Unzipping the Code of Life: Scientists Pinpoint Where DNA First Opens
Researchers mapped where DNA first opens and how a helicase gate may release one strand as genome copying begins. Before a cell can divide, it must open its tightly wound DNA and begin copying the entire [...]
Scientists Tested an 8-Hour Eating Window and Found a Surprising Brain Benefit
Limiting the daily eating window may provide brain benefits beyond those associated with weight loss. Eating within a shorter daily window may provide cognitive benefits beyond those associated with weight loss alone, according to [...]
Focused Ultrasound Opens Blood-Brain Barrier to Treat Brain Cancer
Summary: A new study demonstrates that primary brain tumors (gliomas) are particularly receptive to targeted drug delivery using focused ultrasound (FUS) combined with microbubbles. The team developed a high-resolution MRI protocol to track blood-brain barrier [...]
AI’s promise and practical limits in drug discovery
AI tools are becoming increasingly common in early drug discovery, allowing scientists to analyse data and navigate large volumes of research. However, according to Dr Raminderpal Singh, turning that potential into consistent scientific workflows [...]
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
Healthcare Headlines: Challenges and Advances in 2026
Health-related updates reveal financial adjustments by Universal Health Services due to Medicaid reimbursement uncertainties, significant pollution-linked health concerns from French-British oil firm Perenco in Congo, drug trial setbacks, potential restructuring at major medical firms, [...]
