Base-Editing and Gene-Silencing Approaches to Lipid Lowering: A One-Off Treatment and a Lifetime of Consent

Abstract

For three decades, lowering low-density lipoprotein cholesterol (LDL-C) has meant a drug the patient keeps taking:
a daily statin, a twice-monthly injectable antibody, or -- most recently -- a twice-yearly small interfering RNA (siRNA)
injection. Two technologies now promise something categorically different. In vivo CRISPR base editing aims to
permanently disable the PCSK9 gene in the liver with a single intravenous infusion, so that no further treatment, and no
further adherence, is ever required. Long-acting gene silencing with siRNA -- already approved and in wide use as inclisiran --
achieves a similar reduction in circulating PCSK9 protein without touching the gene itself, and its effect fades if the
patient stops returning for injections. Both approaches target the same protein and report broadly similar percentage
reductions in LDL-C, which makes it tempting to treat them as interchangeable options separated only by dosing schedule.