In its first tough test, CRISPR base editing slashes cholesterol levels in monkeys
Aform of CRISPR widely expected to be safer and possibly more effective that the original has aced its first substantive test. When CRISPR “base editing” was used to knock out two cholesterol-associated genes in monkeys, the animals’ blood levels of heart-disease-causing LDL (“bad”) cholesterol and triglycerides plunged as much as 60% and 65%, respectively, Sekar Kathiresan, co-founder and CEO of Verve Therapeutics, announced on Saturday at the (virtual) meeting of the International Society for Stem Cell Research.
The results, from Verve’s experiments in 14 cynomolgus monkeys (a.k.a. crab-eating macaques), are the first published data showing successful CRISPR base editing in a non-human primate; there have been similar successes in mice. They are therefore good news not only for Verve, which was founded last year to develop CRISPR-based cures for cardiovascular disease, but also for Beam Therapeutics, a two-year-old company developing CRISPR base editors for a long list of diseases. Verve licensed Beam’s “adenine base editor” for its experiment.
“Our goal is to develop a one-and-done genome editing medicine for heart disease,” Kathiresan told STAT ahead of his ISSCR talk.
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The base editors targeted one of two genes that both monkeys and people have: PCSK9 and ANGPTL3. In 2006, scientists discovered that one broken copy of PCSK9, a gene that makes an enzyme involved in cholesterol metabolism, causes a 28% reduction in an individual’s mean LDL cholesterol (compared to people with two working copies of the gene) and an 88% reduction in lifetime risk of coronary artery disease. About 1 in 50 people have at least one disabled PCSK9. When ANGPTL3 is disabled, scientists discovered in 2010, triglycerides are also at rock-bottom levels and the lifetime risk of heart attack is reduced by 34%. About 1 in 300 people have a mutation that disables at least one of their copies of ANGPTL3.
Both genes are expressed in the liver, so that’s where Verve’s scientists sent their base editor (enclosed in a lipid nanoparticle). “The idea is to confer, with base editing, the protection that some rare people have naturally,” Kathiresan said.
https://www.statnews.com/2020/06/27/crispr-base-editing-slashes-cholesterol-in-monkeys/
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