Researchers at the University of Houston School of Pharmacy have discovered an unexpectedly simple strategy for improving the performance of mRNA vaccines and gene therapy drugs: the addition of salt. The findings, published in the journal Small, solve one of the biggest challenges facing modern genetic medicine: delivering fragile therapeutic materials to the right places inside cells.
We introduce salt-loaded lipid nanoparticles as a novel and widely applicable design principle for gene delivery. What’s interesting about this is that it doesn’t require inventing entirely new materials and can significantly improve delivery efficiency. ”
Fanfei Meng, Assistant Professor and Presidential Frontier Faculty, Department of Pharmacology and Pharmacy
Lipid nanoparticles (LNPs) are small fat-based delivery vehicles that are widely used to transport fragile genetic material into cells. These became widely recognized during the coronavirus pandemic through the mRNA vaccines developed by Moderna and Pfizer. Scientists are currently using LNPs to develop new treatments for cancer, rare diseases, and genetic disorders.
Despite their success, major obstacles remain. Once in the cell, much of the therapeutic cargo is trapped within endosomes. Endosomes are membrane-enclosed compartments that prevent genetic material from reaching the interior of the cell for proper functioning.
Researchers have long considered this “endosomal escape” problem to be one of the major bottlenecks limiting the effectiveness of mRNA vaccines and other gene-based medicines.
“Many gene therapies fail for this reason,” Meng says. “We’ve discovered a surprisingly easy way to help you get more cargo out of the way.”
escape plan
Meng and his research team found that loading lipid nanoparticles with salt creates pressure within endosomes, which helps release and activate therapeutic substances into cells. The research team believes this strategy could ultimately help improve a wide range of treatments, including mRNA vaccines, gene editing techniques, and other nucleic acid-based therapies.
This approach relies on basic physical principles rather than complex chemical redesign, making it easier to adapt to future therapeutics and large-scale manufacturing.
“We found that instead of redesigning the nanoparticle itself, we could fundamentally improve intracellular delivery by controlling the ionic environment,” Meng said. “This method is simple and scalable and has great potential as the next generation of RNA and gene-based medicines.”
As interest in genetic medicine continues to grow around the world, Meng said their findings could provide practical new avenues to make these treatments more efficient and accessible.
Meng’s research team includes Cao Thuy Giang Nguyen and Hoang Quang Truong from the University of Massachusetts Lowell. From UH we have Yanhao Li and Urmila Kafre.
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Reference magazines:
C.T.G., Nguyen; Others. (2026). Osmotically driven lipid nanoparticles enable potent cytosolic delivery of nucleic acids. small. DOI: 10.1002/smll.202514547. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202514547
