PCSK9 Base Editing, In Vivo Gene Therapy, and Durable LDL-C Lowering: Scoping Review with ☸️SAIMSARA.

Name: SAIMSARA Evidence Object vascular::PCSK9_BASE_EDITING_SS
Creator: SAIMSARA
License: https://saimsara.com/license/

SAIMSARA

doi:10.62487/saimsarabcdd5697

SAIMSARA Journal

Machine-Readable Science • ISSN 3054-3991

PCSK9 Base Editing, In Vivo Gene Therapy, and Durable LDL-C Lowering: Scoping Review with ☸️SAIMSARA.

Cardiac & Vascular Health

Issue 1, Volume 1, 2026

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DOI: 10.62487/saimsarabcdd5697

Editorial note

• Last update: 2026-05-29 07:15:02

What is this paper about

PCSK9 base editing is moving from experimental promise toward clinical reality, with single-dose therapies already producing durable LDL-C reductions in both primates and early human studies. The full evidence map reveals which delivery platforms, editing strategies, and safety signals are driving this transition—and where the remaining uncertainties still lie.

Human-verified editorial review Verified by World ID proof-of-human. This editorial layer was submitted from a SAIMSARA account verified as a unique human.

Abstract: The aim of this scoping review is to synthesize the current preclinical and clinical evidence surrounding PCSK9 base editing, focusing on delivery vehicles, editing efficiencies, therapeutic durability, and safety profiles across diverse biological substrates. The review uses 51 references and builds its evidence map from 89 original studies with 2172 total participants/sample observations (topic-deduplicated ΣN). The mapped evidence indicates that single-dose PCSK9 base editing is emerging as a durable, potentially curative strategy for lowering circulating PCSK9 and LDL-C, with nonhuman-primate studies showing up to 70% liver editing and sustained LDL-C reductions near 69% beyond a year. Early human data from HeFH patients, including sustained PCSK9 and LDL-C reductions of 74.4% and 52.3%, respectively, at 24 weeks in the 0.6 mg/kg YOLT-101 cohort, support translational feasibility and align with preclinical signals. Across platforms, adenine base editors delivered via LNP, AAV, and GalNAc-LNP converge on premature stop-codon strategies with favorable off-target profiles. However, the limited size and duration of human exposure remain the principal uncertainty. Future work should prioritize multi-year clinical follow-up in larger, more diverse cohorts to confirm safety, genomic stability, and the durability of LDL-C lowering.
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Keywords: PCSK9; Base editing; Adenine base editors; Lipid nanoparticles; Hypercholesterolemia; LDL cholesterol; Gene therapy; In vivo gene editing; Cardiovascular disease; Cholesterol reduction

Review Stats

Final search date and database lock: 2026-05-20 20:09:35 CEST
Plan: Pro (expanded craft tokens; source: Semantic Scholar)
Source: Semantic Scholar
Total Abstracts/Papers: 110440
Downloaded Abstracts/Papers: 1000
Included original and non-original Abstracts/Papers (all): 125
Included original Abstracts/Papers (Vote counting by direction of effect): 89
Reference Index (links used in paper): 51
Total participants/sample observations (topic deduplicated ΣN): 2172

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Reference Index (51)

[1] Abstract 4139206: Design of Heart-2: a phase 1b clinical trial of VERVE-102, an in vivo base editing medicine delivered by a GalNAc-LNP and targeting PCSK9 to durably lower LDL cholesterol — https://doi.org/10.1161/circ.150.suppl_1.4139206
[2] In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels — https://doi.org/10.1038/s41587-021-00933-4
[3] Efficacy and Safety of an Investigational Single-Course CRISPR Base-Editing Therapy Targeting PCSK9 in Nonhuman Primate and Mouse Models — https://doi.org/10.1161/circulationaha.122.062132
[4] In vivo base editing gene therapy for heterozygous familial hypercholesterolemia: a phase 1 trial — https://doi.org/10.1038/s41591-026-04254-4
[5] In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model — https://doi.org/10.1186/s12915-018-0624-2
[6] Minimizing the ratio of ionizable lipid in lipid nanoparticles for in vivo base editing — https://doi.org/10.1093/nsr/nwae135
[7] In Vivo Base Editing of PCSK9 as a Therapeutic Alternative to Genome Editing — https://doi.org/10.1161/atvbaha.117.309881
[8] Engineering miniature CRISPR-Cas Un1Cas12f1 for efficient base editing — https://doi.org/10.1016/j.omtn.2024.102201

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