Article type:
Research
Estimated read time:
2 mins min read
Published:
29/04/2025
Scientists created a new type of small particle that can safely deliver genetic instructions (mRNA) directly to the lungs. These particles worked better than older systems, helping treat lung cancer in mice, restoring a key protein in cystic fibrosis, and even performing gene editing. This breakthrough could lead to new treatments for serious lung diseases in the future.
Why it Matters This approach shows a major advance in safe, repeatable, and versatile lung-targeted mRNA therapy. Unlike many systems that only handle certain mRNA sizes, this platform worked across a broad range of applications—from immunotherapy to genetic disease correction—while keeping toxicity low.
Hope for the Future The platform holds promise for treating cystic fibrosis, enhancing cancer immunotherapy, and enabling in vivo gene editing in the lungs. Further optimization, such as using biodegradable backbones or refining targeting, could accelerate translation to clinical therapies.
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Background Delivering mRNA to the lungs could transform treatments for diseases such as cystic fibrosis, lung cancer, and infectious diseases. However, existing non-viral systems often suffer from toxicity, immune reactions, or poor efficiency. Polyethylenimine (PEI) has long been studied as a gene delivery material, but balancing safety and effectiveness has been challenging.
What the Study Found The researchers developed a new class of modified PEI-based nanoparticles using a “split-Ugi” chemical reaction. These nanoparticles, when combined with lipids, selectively delivered mRNA to lung cells after intravenous injection. The system (U155@lipids) outperformed standard PEI formulations, enabling:
- Expression of both small (IL-12) and large (CFTR) therapeutic mRNAs.
- Effective tumor suppression in a lung cancer model via IL-12 delivery.
- Restoration of chloride channel activity in cystic fibrosis models using CFTR mRNA.
- Functional in vivo gene editing with CRISPR-Cas9.
Citation Vlasova KY et al., Nat Commun. 2025 16(1):4021.
Authors Vlasova KY, Kerr A, Pennock ND, Jozic A, Sahel DK, Gautam M, Murthy NTV, Roberts A, Ali MW, MacDonald KD, Walker JM, Luxenhofer R, Sahay G
Date of publication 29/4/25