In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates.
Level 5 - mechanism / opinion, no new human data
Preclinical in vivo animal study (nonhuman primates)
PubMed 34012082 · doi:10.1038/s41586-021-03534-y
What was done
Researchers delivered CRISPR base editors targeting the *PCSK9* gene into cynomolgus monkeys (*Macaca fascicularis*) via a single in vivo infusion of lipid nanoparticles. Hepatic gene knockdown and circulating levels of PCSK9 and low-density lipoprotein (LDL) cholesterol were tracked for at least 8 months post-infusion.
What was found
A single lipid nanoparticle infusion led to near-complete knockdown of PCSK9 in the liver. This produced an approximate 90% reduction in circulating blood PCSK9 and an approximate 60% reduction in blood LDL cholesterol, with both reductions persisting stably for at least 8 months.
Why it matters
This demonstrates durable in vivo base editing in nonhuman primates, supporting a potential single-treatment strategy for long-term LDL cholesterol lowering to address atherosclerotic cardiovascular disease.
Limits
The findings are from nonhuman primates and cannot directly establish human clinical safety or efficacy. The abstract does not disclose the sample size, statistical variance or confidence intervals, off-target editing rates, or potential toxicities. Follow-up was limited to at least 8 months.
Cited by
- supports CRISPR gene editing of the PCSK9 gene in the liver of monkeys achieved a 60% reduction in LDL cholesterol levels.