East Montgomery Times

A new development in gene therapy could significantly impact the treatment of chronic diseases such as heart disease, diabetes, and cancer. Researchers at the Perelman School of Medicine at the University of Pennsylvania have advanced a method to deliver therapeutic DNA into cells using lipid nanoparticles (LNPs). This innovation aims to improve the process of activating DNA instructions within cells, crucial for combating diseases. The findings were published in Nature Biotechnology.

The research builds on previous work involving messenger RNA (mRNA) therapies used in COVID-19 vaccines. Jake Brenner, MD, PhD, an assistant professor of Medicine and Pharmacology, stated: “For 20 years, DNA delivery with LNPs has been a major goal in this field.” He added that they are continuing from where mRNA left off to address more significant challenges.

While mRNA therapies have shown promise, they degrade quickly and struggle to target specific cell types effectively. In contrast, DNA can remain active for extended periods and be programmed for targeted cell activity. However, earlier attempts to use LNPs for DNA delivery faced safety issues due to severe immune reactions.

Brenner’s team identified that previous failures were due to LNPs triggering an inflammatory response via the STING pathway. By incorporating nitro-oleic acid (NOA), a natural anti-inflammatory molecule, into the DNA-carrying particles, researchers eliminated fatal reactions seen in prior tests. Laboratory experiments showed that mice survived with this improved system.

This advancement allows treated cells to produce therapeutic proteins for about six months from a single dose—significantly longer than mRNA therapies' few hours. Compared to viral methods used in gene therapy, these DNA-LNPs can carry larger genetic instructions with fewer immune reactions and more precise targeting capabilities.

Brenner remarked: “This technology holds incredible promise—not just to treat diseases but to fundamentally change how we address health challenges that affect millions.”

Future studies will focus on refining this technology further and testing its effectiveness across various tissues and disease models.

The research received funding support from the American Heart Association and the National Institute for Health.