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Scientists at the University of Texas Southwestern Medical Center have developed a novel lipid nanoparticle (LNP) delivery system that shows promise for treating cystic fibrosis (CF) and other genetic diseases.
Published in Science, the research led by Daniel Siegwart focuses on delivering gene-editing tools, like CRISPR, directly to lung cells, including stem cells. Current treatments, such as Trikafta, only target specific CF mutations, leaving many patients without effective therapies. The goal of this study was to explore new ways to correct these genetic mutations.
The researchers used engineered LNPs to deliver the CRISPR machinery intravenously, bypassing the thick mucus that often impairs delivery via inhalation. They used a technique called selective organ targeting (SORT), which allowed the LNPs to target specific organs, in this case, the lungs. When injected into mice, the LNPs delivered gene-editing tools to a broad range of lung cells, resulting in long-lasting gene correction. After 22 months, the edits were still present in 45-80% of stem cells, highlighting the durability of this method.
The team also tested the system on lung cells from CF patients with mutations resistant to current treatments. The CRISPR-based edits corrected the mutation and restored CFTR protein function, with minimal off-target effects, as confirmed by DNA sequencing. The LNPs were found to be enriched with vitronectin, a protein that helps them home in on lung cells.
This research represents a significant step forward in gene therapy, potentially offering a single-treatment cure for CF. However, as Siegwart noted, clinical trials are still far off, and more testing in higher animals is needed before moving to human applications. If successful, this method could lead to a lifelong cure for CF and other genetic disorders.
