ArticleNature biotechnology2018
Meganuclease targeting of PCSK9 in macaque liver leads to stable reduction in serum cholesterol.
Article in Nature biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
80 citing papers in PubMed, 122 citations in OpenAlex.
- Monitoring Fetal Somatic Cell Genome EditingHuman gene therapy · 2026Article
- A Focused Comparative Review of Innovative Therapeutics Across Autoimmune and Chronic Inflammatory Diseases.Life (Basel, Switzerland) · 2026Review
- Molecular mechanisms of PCSK9 in cardiology: therapeutic implications and clinical impacts on the cardiorenal axis.Molecular and cellular biochemistry · 2026Review
- Toward an Integrated Therapeutic Approach for Familial Hypercholesterolemia.Current medical science · 2026Review
- Genetic determinants of lipid metabolism in cardioprotection: From mechanisms to clinical practice.Biomolecules & biomedicine · 2025Review
- Organoids in Genetic Disorders: from Disease Modeling to Translational Applications.Stem cell reviews and reports · 2025Review
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- RHO1-2 meganuclease gene editing targets human P23H rhodopsin-induced retinitis pigmentosa to rejuvenate rods and maintain cones.bioRxiv : the preprint server for biology · 2025Article
- High-efficiency homology-directed insertion into the genome using the engineered homing endonuclease ARCUS.Nucleic acids research · 2025Article
- Gene Therapy Approaches for Atherosclerosis Focusing on Targeting Lipid Metabolism and Inflammation.International journal of molecular sciences · 2025Review
- Engineering of extracellular vesicles for efficient intracellular delivery of multimodal therapeutics including genome editors.Nature communications · 2025Article
- Branched endosomal disruptor (BEND) lipids mediate delivery of mRNA and CRISPR-Cas9 ribonucleoprotein complex for hepatic gene editing and T cell engineering.Nature communications · 2025Article
- Harnessing mRNA for heart health: a new era in cardiovascular treatment.Theranostics · 2025Review
- Gene Editing: An Effective Tool for the Future Treatment of Kidney Disease.Journal of inflammation research · 2025Review
- The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer's Disease: A Possible Target for the Disease Treatment.International journal of molecular sciences · 2024Review
- A temperature-sensitive and less immunogenic Sendai virus for efficient gene editing.Journal of virology · 2024Article
- Optimization of the activity and biodegradability of ionizable lipids for mRNA delivery via directed chemical evolution.Nature biomedical engineering · 2024Article
- Fast and facile synthesis of amidine-incorporated degradable lipids for versatile mRNA delivery in vivo.Nature chemistry · 2024Article
- Influence of ionizable lipid tail length on lipid nanoparticle delivery of mRNA of varying length.Journal of biomedical materials research. Part A · 2024Article
- Therapeutic Gene Editing in Dyslipidemias.Reviews in cardiovascular medicine · 2024Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical translation of in vivo genome editing to treat human genetic diseases requires thorough preclinical studies in relevant animal models to assess safety and efficacy. A promising approach to treat hypercholesterolemia is inactivating the secreted protein PCSK9, an antagonist of the LDL receptor. Here we show that single infusions in six non-human primates of adeno-associated virus vector expressing an engineered meganuclease targeting PCSK9 results in dose-dependent disruption of PCSK9 in liver, as well as a stable reduction in circulating PCSK9 and serum cholesterol. Animals experienced transient, asymptomatic elevations of serum transaminases owing to the formation of T cells against the transgene product. Vector DNA and meganuclease expression declined rapidly, leaving stable populations of genome-edited hepatocytes. A second-generation PCSK9-specific meganuclease showed reduced off-target cleavage. These studies demonstrate efficient, physiologically relevant in vivo editing in non-human primates, and highlight safety considerations for clinical translation.
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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.