ArticleJournal of extracellular vesicles2024
Extracellular vesicle-mediated delivery of CRISPR/Cas9 ribonucleoprotein complex targeting proprotein convertase subtilisin-kexin type 9 (Pcsk9) in primary mouse hepatocytes.
Article in Journal of extracellular vesicles, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Overview of Delivery Methods for Gene Editing.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Recent Advances in Non-Viral Vectors for Gene Therapy and Gene Delivery: From Lipid Nanoparticles to Engineered Extracellular Vesicles.Pharmaceutics · 2026Review
- Beyond Permanent Genome Editing: Molecular Delivery Strategies for RNA Editing and Epigenome-Editing Therapeutics.International journal of molecular sciences · 2026Review
- IDMME and IDMDE: inducible CRISPR-dCasRx platforms for spatiotemporal RNA mGenome biology · 2026Article
- Engineering challenges and translational opportunities in emerging gene delivery platforms.Nature biomedical engineering · 2026Review
- Engineered Extracellular Vesicles for Treatment of Inflammatory Diseases.Molecular biotechnology · 2026Review
- Advancing the Landscape of RNAi Nanotherapeutics for Ischemic Heart Disease.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Article
- Bioengineering of extracellular vesicles with scaffold proteins for drug delivery.Journal of nanobiotechnology · 2026Review
- Extracellular vesicle-mediated delivery of CRISPR machinery silences androgen receptor in castration-resistant prostate cancer cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- Extracellular vesicles in cardiovascular homeostasis and disease: potential role in diagnosis and therapy.Nature reviews. Cardiology · 2025Review
- Harnessing extracellular vesicles to deliver genetic medicine for cardiac repair.Nanomedicine (London, England) · 2025Article
- Gene Therapy Approaches for Atherosclerosis Focusing on Targeting Lipid Metabolism and Inflammation.International journal of molecular sciences · 2025Review
- Versatile tethering system to control cell-specific targeting of bioengineered extracellular vesicles.Scientific reports · 2025Article
- Engineered extracellular vesicles as imaging biomarkers and therapeutic applications for urological diseases.Materials today. Bio · 2025Review
- Advancements in CRISPR/Cas systems for disease treatment.Acta pharmaceutica Sinica. B · 2025Review
- Surface-modified extracellular vesicles take their chance in the big PCSK9 inhibitors' race.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Expanding the CRISPR/Cas toolkit: applications in proteomics and theranostics.Frontiers in bioengineering and biotechnology · 2025Review
- Anti-cancer compound screening identifies Aurora Kinase A inhibition as a means to favor CRISPR/Cas9 gene correction over knock-out.PloS one · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
The loss-of-function of the proprotein convertase subtilisin-kexin type 9 (Pcsk9) gene has been associated with significant reductions in plasma serum low-density lipoprotein cholesterol (LDL-C) levels. Both CRISPR/Cas9 and CRISPR-based editor-mediated Pcsk9 inactivation have successfully lowered plasma LDL-C and PCSK9 levels in preclinical models. Despite the promising preclinical results, these studies did not report how vehicle-mediated CRISPR delivery inactivating Pcsk9 affected low-density lipoprotein receptor recycling in vitro or ex vivo. Extracellular vesicles (EVs) have shown promise as a biocompatible delivery vehicle, and CRISPR/Cas9 ribonucleoprotein (RNP) has been demonstrated to mediate safe genome editing. Therefore, we investigated EV-mediated RNP targeting of the Pcsk9 gene ex vivo in primary mouse hepatocytes. We engineered EVs with the rapamycin-interacting heterodimer FK506-binding protein (FKBP12) to contain its binding partner, the T82L mutant FKBP12-rapamycin binding (FRB) domain, fused to the Cas9 protein. By integrating the vesicular stomatitis virus glycoprotein on the EV membrane, the engineered Cas9 EVs were used for intracellular CRISPR/Cas9 RNP delivery, achieving genome editing with an efficacy of ±28.1% in Cas9 stoplight reporter cells. Administration of Cas9 EVs in mouse hepatocytes successfully inactivated the Pcsk9 gene, leading to a reduction in Pcsk9 mRNA and increased uptake of the low-density lipoprotein receptor and LDL-C. These readouts can be used in future experiments to assess the efficacy of vehicle-mediated delivery of genome editing technologies targeting Pcsk9. The ex vivo data could be a step towards reducing animal testing and serve as a precursor to future in vivo studies for EV-mediated CRISPR/Cas9 RNP delivery targeting Pcsk9.
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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.