Researchers at UT Southwestern Medical Center have successfully used lipid nanoparticles—microscopic fat-based carriers—to deliver gene therapy that repairs DNA in the lungs and liver of mice with alpha-1 antitrypsin deficiency. This marks a major step toward treating the rare inherited disease in humans. The study, published in Nature Biotechnology, used nanoparticles to deliver gene-editing tools directly to target organs.
Targeting Both Lungs and Liver
As reported by medicalxpress, Alpha-1 antitrypsin deficiency stems from mutations in the SERPINA1 gene, causing misfolded proteins to damage both the liver and lungs. While traditional lipid nanoparticles typically accumulate in the liver, researchers added a fifth lipid called DORI, which redirected the particles to the lungs. This innovation allowed for simultaneous correction in both organs—a challenge that had long hindered gene therapy efforts.
Impressive Results in Mice
Using base editors to fix the Z variant of the mutated gene, researchers corrected DNA in approximately 40% of liver cells and 10% of lung cells. These corrected cells significantly restored normal liver and lung function—by over 80% and 90%, respectively. The gene-editing effects lasted for at least 32 weeks, offering hope for lasting therapeutic impact.
Looking Ahead: Broader Applications
While companies like Beam Therapeutics are developing liver-targeted therapies, experts believe that directly correcting lung cells could be equally crucial. Study leader Dr. Daniel Siegwart aims to test this approach in larger animal models. His startup, ReCode Therapeutics, is already developing similar therapies for cystic fibrosis and primary ciliary dyskinesia. With FDA Orphan Drug Designation secured for one of their therapies, the potential to treat multiple rare respiratory diseases is growing rapidly.