ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Non-viral Delivery of Zinc Finger Nuclease mRNA Enables Highly Efficient In Vivo Genome Editing of Multiple Therapeutic Gene Targets.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- CCR5-edited CD4+ T cells augment HIV-specific immunity to enable post-rebound control of HIV replication.The Journal of clinical investigation · 2021Trial
- Design of optimized epigenetic regulators for durable gene silencing with application to PCSK9 in nonhuman primates.Nature biotechnology · 2026Article
- Review
- RNA-LNP-mediated in vivo prime editing corrects disease phenotypes in a mouse model of citrullinemia type I.Science translational medicine · 2026Article
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Spatial profiling of gene editing by in situ sequencing in mice and macaques.Nature biomedical engineering · 2026Article
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Unlocking mRNA-driven CRISPR-Cas9 gene therapy via optimizing mRNA and the delivery vectors.Molecular therapy. Nucleic acids · 2025Review
- Treatment of a metabolic liver disease in mice with a transient prime editing approach.Nature biomedical engineering · 2025Article
- Application of Gene Editing Technology Based on Targeted Delivery Materials in TNBC.ACS omega · 2025Review
- Research progress of mRNA vaccines for infectious diseases.European journal of medical research · 2025Review
- Serum factors create species-specific barriers to hepatic gene transfer by lipid nanoparticles in liver-humanized mice.Molecular therapy. Methods & clinical development · 2025Article
- Lipid nanoparticle delivery of TALEN mRNA targeting LPA causes gene disruption and plasma lipoprotein(a) reduction in transgenic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Lipid-based Non-viral Vector: Promising Approach for Gene Delivery.Current pharmaceutical design · 2025Review
- Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders.Acta pharmaceutica Sinica. B · 2024Review
- Review
- Precise genome-editing in human diseases: mechanisms, strategies and applications.Signal transduction and targeted therapy · 2024Review
- The mixing method used to formulate lipid nanoparticles affects mRNA delivery efficacy and organ tropism.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2023Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has previously been shown that engineered zinc finger nucleases (ZFNs) can be packaged into adeno-associated viruses (AAVs) and delivered intravenously into mice, non-human primates, and most recently, humans to induce highly efficient therapeutic genome editing in the liver. Lipid nanoparticles (LNPs) are synthetic delivery vehicles that enable repeat administration and are not limited by the presence of preexisting neutralizing antibodies in patients. Here, we show that mRNA encoding ZFNs formulated into LNP can enable >90% knockout of gene expression in mice by targeting the TTR or PCSK9 gene, at mRNA doses 10-fold lower than has ever been reported. Additionally, co-delivering mRNA-LNP containing ZFNs targeted to intron 1 of the ALB locus with AAV packaged with a promoterless human IDS or FIX therapeutic transgene can result in high levels of targeted integration and subsequent therapeutically relevant levels of protein expression in mice. Finally, we show repeat administration of ZFN mRNA-LNP after a single AAV donor dose results in significantly increased levels of genome editing and transgene expression compared to a single dose. These results demonstrate LNP-mediated ZFN mRNA delivery can drive highly efficient levels of in vivo genome editing and can potentially offer a new treatment modality for a variety of diseases.
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Registered trials
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.