Gene therapy in the lungs could treat a range of devastating illnesses, but lack of safe and efficient delivery has held back the field. Here, in silico screening of millions of lipid nanoparticles (LNPs) yielded several chemically novel and highly potent LNPs for pulmonary gene therapy.
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References
Pearson, H. Hunan genetics: one gene, twenty years. Nature 460, 164–169 (2009). A history of the discovery of CFTR as the gene mutated in CF and early efforts to treat CF with gene therapy.
Witten, J., Hu, Y., Langer, R. & Anderson, D. G. Recent advances in nanoparticulate RNA delivery systems. Proc. Natl Acad. Sci. USA 121, e2307798120 (2024). A review article of current preclinical and clinical RNA delivery efforts.
Rhym, L. H., Manan, R. S., Koller, A., Stephanie, G. & Anderson, D. G. Peptide-encoding mRNA barcodes for the high-throughput in vivo screening of libraries of lipid nanoparticles for mRNA delivery. Nat. Biomed. Eng. 7, 901–910 (2023). A new approach to in vivo barcode-based LNP screening that can screen dozens of LNPs in a single animal.
Tang, Y., Yan, Z. & Engelhardt, J. Viral vectors, animal models, and cellular targets for gene therapy of cystic fibrosis lung disease. Hum. Gene. Ther. 31, 524–537 (2020). A review article that discusses different animal models of the lung and how they can be used to test gene therapies for CF.
Jiang, A. Y. et al. Combinatorial development of nebulized mRNA delivery formulations for the lungs. Nat. Nanotechnol. 19, 364–375 (2023). Our work that introduced IR-117-17 and showed potent delivery to mouse conducting airways; the alveolar-only expression we observed here in ferrets shows the importance of large animal model testing.
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This is a summary of: Witten, J. et al. Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02490-y (2024).
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Using artificial intelligence to develop gene therapy for the lungs. Nat Biotechnol (2024). https://doi.org/10.1038/s41587-024-02491-x
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DOI: https://doi.org/10.1038/s41587-024-02491-x
