ArticleNature biomedical engineering2022
Augmented lipid-nanoparticle-mediated in vivo genome editing in the lungs and spleen by disrupting Cas9 activity in the liver.
Article in Nature biomedical engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- Delivering the blueprint: Advances and challenges in mRNA therapeutics for the respiratory system.International journal of pharmaceutics: X · 2026Review
- Hydrophobic Tail and Linker Diversification of PEG-Lipids Unlocks Precise Muscle Tropism of mRNA-Lipid Nanoparticles.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Messenger RNA and guide RNA distributions in lipid nanoparticles impact gene-editing efficiency in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Nanotechnology-mediated precision delivery of mRNA.Nature materials · 2026Review
- Recent advances in the application of polymeric nanoparticles to the pulmonary delivery of mRNA.Nanomedicine (London, England) · 2026Review
- mRNA Lipid Nanoparticles for Cell Engineering in Vivo and in Vitro: Current Applications and Future Directions.MedComm · 2026Review
- A universal and orthogonal safety valve for CRISPR/Cas12a without chemical modification or external stimulation.Nucleic acids research · 2026Article
- Steering spherical nucleic acids over metabolic organs for improved targeted drug delivery.Journal of nanobiotechnology · 2026Review
- Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems.Cell systems · 2025Review
- Structural immunotherapy: Harnessing chemical design to build powerful next-generation therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Glycolipid nanoparticles target the spleen and detarget the liver without charge.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting and tracking mRNA lipid nanoparticles at the particle, transcript and protein level.Nature biomedical engineering · 2025Review
- Review
- Synthesis of ionizable lipopolymers using split-Ugi reaction for pulmonary delivery of various size RNAs and gene editing.Nature communications · 2025Article
- Specific macrophage RhoA targeting CRISPR-Cas9 for mitigating osteoclastogenesis-induced joint damage in inflammatory arthritis.Cell reports. Medicine · 2025Article
- Metabolic Stability and Targeted Delivery of Oligonucleotides: Advancing RNA Therapeutics Beyond The Liver.Journal of medicinal chemistry · 2025Review
- Ionizable polymeric micelles (IPMs) for efficient siRNA delivery.Nature communications · 2025Article
- Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects.International journal of molecular sciences · 2024Review
- Exploring the potential of cell-derived vesicles for transient delivery of gene editing payloads.Advanced drug delivery reviews · 2024Review
- Lung-Specific mRNA Delivery Enabled by Sulfonium Lipid Nanoparticles.Nano letters · 2024Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemically delivered lipid nanoparticles are preferentially taken up by hepatocytes. This hinders the development of effective, non-viral means of editing genes in tissues other than the liver. Here we show that lipid-nanoparticle-mediated gene editing in the lung and spleen of adult mice can be enhanced by reducing Cas9-mediated insertions and deletions in hepatocytes via oligonucleotides disrupting the secondary structure of single-guide RNAs (sgRNAs) and also via their combination with short interfering RNA (siRNA) targeting Cas9 messenger RNA (mRNA). In SpCas9 mice with acute lung inflammation, the systemic delivery of an oligonucleotide inhibiting an sgRNA targeting the intercellular adhesion molecule 2 (ICAM-2), followed by the delivery of the sgRNA, reduced the fraction of ICAM-2 indels in hepatocytes and increased that in lung endothelial cells. In wild-type mice, the lipid-nanoparticle-mediated delivery of an inhibitory oligonucleotide, followed by the delivery of Cas9-degrading siRNA and then by Cas9 mRNA and sgRNA, reduced the fraction of ICAM-2 indels in hepatocytes but not in splenic endothelial cells. Inhibitory oligonucleotides and siRNAs could be used to modulate the cell-type specificity of Cas9 therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.