ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Long-term stable reduction of low-density lipoprotein in nonhuman primates following in vivo genome editing of PCSK9.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 55 citations in OpenAlex.
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Therapeutic precision gene editing of cholesterol pathways as a gene therapy strategy for cardiovascular disease.Gene therapy · 2026Review
- Molecular mechanisms of PCSK9 in cardiology: therapeutic implications and clinical impacts on the cardiorenal axis.Molecular and cellular biochemistry · 2026Review
- Review
- Review
- Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development.Biomolecules & therapeutics · 2026Review
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Gene therapy then and now: A look back at changes in the field over the past 25 years.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Gene editing therapy as a therapeutic approach for cardiovascular diseases in animal models: A scoping review.PloS one · 2025Article
- Harnessing mRNA for heart health: a new era in cardiovascular treatment.Theranostics · 2025Review
- Non-rodent Models of Atherosclerosis: Repurposing of Existing Drugs and Search for Novel Treatment Strategies.Current cardiology reviews · 2025Review
- Therapeutic Gene Editing in Dyslipidemias.Reviews in cardiovascular medicine · 2024Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Liver directed adeno-associated viral vectors to treat metabolic disease.Journal of inherited metabolic disease · 2024Review
- Efficient elimination of MELAS-associated m.3243G mutant mitochondrial DNA by an engineered mitoARCUS nuclease.Nature metabolism · 2023Article
- Review
- What did CRISPR-Cas9 accomplish in its first 10 years?Biochemia medica · 2023Article
- Applications of Genome Editing Technologies in CAD Research and Therapy with a Focus on Atherosclerosis.International journal of molecular sciences · 2023Review
- Targeting PCSK9 and Beyond for the Management of Low-Density Lipoprotein Cholesterol.Journal of clinical medicine · 2023Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene disruption via programmable, sequence-specific nucleases represents a promising gene therapy strategy in which the reduction of specific protein levels provides a therapeutic benefit. Proprotein convertase subtilisin/kexin type 9 (PCSK9), an antagonist of the low-density lipoprotein (LDL) receptor, is a suitable target for nuclease-mediated gene disruption as an approach to treat hypercholesterolemia. We sought to determine the long-term durability and safety of PCSK9 knockdown in non-human primate (NHP) liver by adeno-associated virus (AAV)-delivered meganuclease following our initial report on the feasibility of this strategy. Six previously treated NHPs and additional NHPs administered AAV-meganuclease in combination with corticosteroid treatment or an alternative AAV serotype were monitored for a period of up to 3 years. The treated NHPs exhibited a sustained reduction in circulating PCSK9 and LDL cholesterol (LDL-c) through the course of the study concomitant with stable gene editing of the PCSK9 locus. Low-frequency off-target editing remained stable, and no obvious adverse changes in histopathology of the liver were detected. We demonstrate similar on-target nuclease activity in primary human hepatocytes using a chimeric liver-humanized mouse model. These studies demonstrate that targeted in vivo gene disruption exerts a lasting therapeutic effect and provide pivotal data for safety considerations, which support 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.