A naukri.com initiative
Bioengineer
5d
57
Image Credit: Bioengineer
Dual SORT LNPs Enable Multi-Organ Base Editing
- Researchers have developed Dual SORT LNPs, a lipid nanoparticle system enabling precise base editing in both the liver and lungs for genetic diseases like Alpha-1 antitrypsin deficiency (AATD). AATD affects liver and lung function due to mutated SERPINA1 gene causing misfolded A1AT proteins and insufficient enzyme inhibition, respectively.
- The innovative base editing strategy addresses the complex pathology of AATD in multiple organs, where conventional therapies have limitations in delivering genetic medicines effectively to diverse tissues.
- Dual SORT LNPs allow efficient co-delivery of base editors to liver and lung cells, achieving significant correction rates in liver and lung AT2 cells essential for AATD pathology.
- The base editing persistence over a 32-week period in liver cells resulted in a substantial reduction of Z-allele A1AT protein levels, normalizing hepatic function and mitigating liver disease progression.
- In the lungs, the correction led to a notable reduction in neutrophil elastase activity, indicating mitigation of pulmonary damage pathways and potential alleviation of emphysema.
- The precise organ targeting of Dual SORT LNPs, with tailored lipid formulations, enhances selective delivery to specific cellular microenvironments, minimizing off-target effects and systemic toxicity.
- This breakthrough paves the way for future applications of dual-organ gene editing therapies, with promising safety profiles and potential for broadening the approach to treat other multi-organ genetic diseases.
- The innovation signifies a paradigm shift in genetic medicine by integrating precision editing with targeted delivery to address systemic diseases effectively, transforming untreatable conditions into manageable or curable illnesses.
- Further optimization of Dual SORT LNPs could involve customization for additional tissues, scale-up of manufacturing, and integration of next-generation base editors to enhance editing precision and scope.
- This groundbreaking technology offers a tangible pathway towards durable cures for complex genetic diseases, reshaping therapeutic genome editing and providing hope for millions affected by multisystemic genetic conditions.
- Author: Researchers Kim, Song, and Chen. Article Title: Dual SORT LNPs for multi-organ base editing. Published in Nature Biotechnology (2025).
Read Full Article
3 Likes
For uninterrupted reading, download the app