CRISPR Editing Lowers LDL Cholesterol in Monkeys
- CRISPR is a technology that has changed the way basic research is conducted and the way we can now think about disease treatment.
- CRISPR can potentially modify genes that cause disease.
- Durable gene editing in target organs of non-human primates is a key step before the administration of gene editor substances to humans.
- Researchers demonstrated that CRISPR editors that are transported using lipid nanoparticles can modify genes that may cause diseases in living monkeys.
- They observed that a gene called PCSK9 in the liver had reduced its expression activity after infusion of lipid nanoparticles.
- PCSK9 is a gene that provides instructions for making a protein associated with the regulation of cholesterol in the blood.
- They also observed approximately 90% reduction of PCSK9 blood levels and about 60% reduction of low-density lipoprotein cholesterol.
- All the changes observed remained stable for more than 8 months after a single-dose treatment.
- The findings support a once-and-done approach to the reductions of LDL cholesterol and the atherosclerotic cardiovascular disease treatment.
- Atherosclerotic cardiovascular disease is the leading cause of death worldwide.
- The results also provide additional evidence for how CRISPR base editors can be applied to make single-nucleotide changes in therapeutic target genes in the liver, and potentially in other organs.
Musunuru, K., Chadwick, A.C., Mizoguchi, T. et al. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature 593, 429–434 (2021). https://doi.org/10.1038/s41586-021-03534-y