New discovery uses salt to overcome major obstacle in gene therapy

Researchers at the University of Houston’s College of Pharmacy have discovered an unexpected simple strategy to improve the performance of mRNA vaccines and gene therapeutics: adding salt. The findings, published in Small, address one of the biggest challenges facing modern gene medicine — getting fragile therapeutic material to the right place inside cells. 

“We are introducing salt-loaded lipid nanoparticles as a novel and broadly applicable design principle for gene delivery,” said Fanfei Meng, assistant professor and Presidential Frontier Faculty member in the Department of Pharmacological and Pharmaceutical Sciences. “What makes this exciting is that we can significantly improve delivery efficiency without needing to invent entirely new materials.” 

Lipid nanoparticles, or LNPs, are tiny fat-based delivery vehicles widely used to transport fragile genetic material into cells. They became widely recognized during the COVID pandemic through mRNA vaccines developed by Moderna and Pfizer. Today, scientists are also using LNPs to develop new treatments for cancer, rare diseases and genetic disorders.  

Despite their success, a major obstacle has remained. After entering cells, much of the therapeutic cargo becomes trapped inside endosomes — membrane-bound compartments that prevent the genetic material from reaching the interior of the cell, where it must go to function properly.  

Researchers have long considered this “endosomal escape” problem one of the major bottlenecks limiting the effectiveness of mRNA vaccines and other gene-based medicines. 

“Many gene therapies fail because of this,” said Meng. “We found a surprisingly simple way to help more of that cargo escape.” 

The escape plan 

Meng and his research team discovered that loading salt into lipid nanoparticles creates pressure inside the endosomes, helping release the therapeutic material into the cell where it can become active. The team believes the strategy could eventually help improve a wide range of treatments, including mRNA vaccines, gene editing technologies and other nucleic acid-based therapeutics. 

The approach relies on basic physical principles rather than complex chemical redesigns, making it easier to adapt for future therapies and large-scale manufacturing. 

“Instead of redesigning the nanoparticle itself, we found that controlling the ionic environment can fundamentally improve delivery inside the cell,” Meng said. “Because this method is simple and scalable, it has strong potential for next-generation RNA and gene-based medicines.” 

As interest in gene medicine continues to grow worldwide, Meng said their findings may offer a practical new path toward making these therapies more efficient and accessible. 

On Meng’s research team are Cao Thuy Giang Nguyen and Hoang Quan Truong from the University of Massachusetts Lowell. From UH are Yanghao Li and Urmila Kafle. 

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