Genome Editing Technology Opens Up New Avenues for Lung Disease Treatment
In the field of life sciences, genome editing technology is advancing to treat genetic diseases. In particular, CRISPR-based genome editing has many possibilities, but it has been challenging to effectively deliver genome editing materials to the lungs. Recent research has developed ionizable lipids derived from amino acids, making it possible to efficiently deliver genome editing materials to lung epithelial cells. This study developed a lipid called CHCha-10 and performed genome editing in a lung disease model in vivo. As a result, genome editing was successfully performed in lung epithelial cells, suggesting a new treatment method for lung diseases. This expands the application range of genome editing technology and contributes to the treatment of various diseases, including lung diseases. Additionally, this study opens up new possibilities in the field of life sciences and accelerates the development of genome editing technology. The results of this study will provide new prospects for the clinical application of genome editing technology and may open up new avenues for disease treatment.
CRISPR-based gene editing holds promise for treating genetic diseases, yet its application to lung disorders has been hindered by the challenges of pulmonary delivery. Inspired by the modularity and biocompatibility of amino acid-derived chemistries, we report the combinatorial synthesis of 960 ionizable lipids incorporating chemically diverse backbones from both proteinogenic and non-proteinogenic ฮฑ-amino acids. Through high-throughput screening and structure-function analysis, we identify CHCha-10, a cyclohexyl amino acid-derived lipid that forms biodegradable nanoparticles capable of efficiently delivering mRNA-based gene editors to lung epithelial cells. Following intratracheal administration, CHCha-10 nanoparticles exhibit enhanced mucus penetration and epithelial-specific transfection in both mice and ferrets. Here, as a functional application, we demonstrate in vivo base editing in the lung via inhalation. Delivery of adenine base editor mRNA and guide RNA targeting the CFTR G542X mutation restores CFTR expression and chloride channel function in G542X human airway epithelial cells, mouse-derived intestinal organoids and the lungs of cystic fibrosis mice. This work establishes a chemically modular design framework for ionizable lipids and a translatable platform for RNA-based pulmonary gene correction.
This study applies genome editing technology to lung diseases, providing a new treatment method. It opens up new possibilities for treating genetic diseases and has significant implications in the field of life sciences. Furthermore, this study will provide new prospects for the clinical application of genome editing technology.