# Precision genome editing als potentieel eenmalige therapie voor hyperlipidemie

*geplaatst 2026-09-28 · Cholesterol · European journal of pharmacology · doi 10.1016/j.ejphar.2026.179312 · https://hartvaat.nl/2026/10/28/precision-genome-editing-als-potentieel-eenmalige-therapie-voor-hyperlipidemie/*

Deze review belicht de transitie van conventionele lipiddaling naar precision genome editing, met name CRISPR-Cas9, base editing en prime editing, als potentieel eenmalige behandeling voor atherosclerose en hyperlipidemie. De auteurs bespreken hoe gerichte bewerking van genen zoals PCSK9 en ANGPTL3 langdurige lipidendaling kan bewerkstelligen, en gaan in op de huidige stand van zaken rond leveringsystemen (AAV's en LNPs), preklinische modellen en veiligheidsvragen. Hoewel de strategie veelbelovend is voor de toekomstige lipidologie, blijft de klinische vertaling op dit moment beperkt door technische uitdagingen en ethische overwegingen.

## English: Precision genome editing strategies for enduring lipid lowering in atherosclerosis.

This narrative review explores the shift from conventional lipid-lowering drugs to precision genome editing (CRISPR-Cas9, base editing, prime editing) as a potential one-time therapy for atherosclerosis and hyperlipidemia. It highlights how targeted editing of lipid-regulating genes like PCSK9 and ANGPTL3 could provide durable cholesterol reduction, while discussing current hurdles in delivery systems (AAVs, LNPs), preclinical modeling, and off-target safety. While highly promising for future lipid management, clinical translation remains distant due to technical and ethical barriers.

## Abstract (original, from the publication)

Atherosclerosis continues to be a primary contributor to global cardiovascular mortality, influenced by intricate lipid and inflammatory mechanisms. Despite the efficacy of conventional pharmacotherapies, ongoing issues of patient non-adherence and residual risk have prompted the exploration of more enduring therapeutic alternatives. This review examines the significant transition in cardiovascular research from conventional, wide knockout models to the utilization of advanced precision genome editing methods, particularly emphasizing CRISPR-Cas9, base editing, and prime editing. These sophisticated molecular tools allow for the accurate insertion and rectification of single-nucleotide variants without causing double-strand breaks, marking a significant shift from rudimentary gene disruption to precise variant engineering. By specifically targeting essential lipid-regulating genes like proprotein convertase subtilisin/kexin type 9 (PCSK9) and angiopoietin-like 3 (ANGPTL3), precision editing presents an exceptional opportunity for lasting, one-shot lipid-lowering treatments. Additionally, we examine the advancement of preclinical modeling, emphasizing humanized models that precisely represent population genetics. This review highlights the essential obstacles to clinical translation, focusing on the optimization of delivery systems such as adeno-associated viruses (AAVs) and lipid nanoparticles (LNPs), as well as the thorough assessment of off-target effects and ethical implications.

Auteurs: Durlav Chowdhury, Nirdesh Singh, Swarnalata Garai, Devi Prasad Pandey, Surendra H Bodakhe

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Bron: European journal of pharmacology, https://doi.org/10.1016/j.ejphar.2026.179312. Bijgewerkt 2026-09-22T00:59:03Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.