This is a very exciting and promising medical trial about a therapy that may permanently cure people of high cholesterol, which is one of the biggest killers in developed countries. It’s permanent...
This is a very exciting and promising medical trial about a therapy that may permanently cure people of high cholesterol, which is one of the biggest killers in developed countries. It’s permanent because it’s permanently changing your DNA.
Patients in the trial received an infusion containing a gene editing “machine,” or a tiny molecular factory wrapped in a cloak of fat. The fat-coated particles travel through the blood directly to the liver, where they are taken up by cells that remove the fatty wrapper.
The editing machine then crawls along the liver cell’s DNA until it finds its target, a gene called PCSK9. It stops there and erases one DNA letter in the gene, replacing it with another.
That simple change disables the PCSK9 gene and prevents cells from making the PCSK9 protein. Without it, the liver pulls more LDL cholesterol out of the bloodstream, keeping the levels lower.
That’s both very cool - that we are starting to have multiple gene-editing therapies - and important. This could potentially be a like a high be like a “vaccine” for high cholesterol. Something you get once and retain protection from for life, unlike lifetime medicines like statins which need to be consumed repeatedly for life.
An exciting medical application! It would save a lot of lives. I was curious how this works on a cellular level. How many cells need to be fixed? Scanning through the journal article, if I'm...
An exciting medical application! It would save a lot of lives.
I was curious how this works on a cellular level. How many cells need to be fixed? Scanning through the journal article, if I'm reading it correctly, it seems like only some cells need to receive the treatment to see a meaningful effect. That's probably much more technically feasible than editing 100% of cells.
Dose-dependent mean reductions in the PCSK9 level ranged from 51% at the 0.3-mg-per-kilogram dose to 88% at the 1.0-mg-per-kilogram dose.
Corresponding reductions in the LDL cholesterol level ranged from 9% at the 0.3-mg-per-kilogram dose to 62% at the 1.0-mg-per-kilogram dose, with an absolute reduction of 78 mg per deciliter at the highest dose.
That seems to measure the protein levels rather than counting cells, but it seems to line up with previous research. (I guess it's not exactly 1:1.)
Liver biopsies 14 days after dosing noted mean PCSK9 editing of 46% and 70% in monkeys treated with VERVE-101 at 0.75 and 1.5 mg/kg, respectively.
This translated into mean reductions in blood PCSK9 (proprotein convertase subtilisin/kexin type 9) of 67% and 83% and reductions of low-density lipoprotein cholesterol of 49% and 69% at the 0.75 and 1.5 mg/kg doses, respectively, assessed as time-weighted average change from baseline between day 28 and up to 476 days after dosing.
The new article says, "Reductions appeared to be durable throughout follow-up, which was at least 1 year in 15 participants." I'd be curious to see if it holds up after 10 years. When the edited cells undergo mitosis, the updated gene is replicated too, so the overall ratio of old-DNA to new-DNA cells remains constant over time. I guess follow-up infusions would only be necessary if something about the alteration affects cell health or division rate unexpectedly.
This is a very exciting and promising medical trial about a therapy that may permanently cure people of high cholesterol, which is one of the biggest killers in developed countries. It’s permanent because it’s permanently changing your DNA.
That’s both very cool - that we are starting to have multiple gene-editing therapies - and important. This could potentially be a like a high be like a “vaccine” for high cholesterol. Something you get once and retain protection from for life, unlike lifetime medicines like statins which need to be consumed repeatedly for life.
An exciting medical application! It would save a lot of lives.
I was curious how this works on a cellular level. How many cells need to be fixed? Scanning through the journal article, if I'm reading it correctly, it seems like only some cells need to receive the treatment to see a meaningful effect. That's probably much more technically feasible than editing 100% of cells.
Vafai et al. 2026, "In Vivo Base Editing of PCSK9 with VERVE-102 for Hypercholesterolemia"
That seems to measure the protein levels rather than counting cells, but it seems to line up with previous research. (I guess it's not exactly 1:1.)
Lee et al. (2022), "Efficacy and Safety of an Investigational Single-Course CRISPR Base-Editing Therapy Targeting PCSK9 in Nonhuman Primate and Mouse Models"
The new article says, "Reductions appeared to be durable throughout follow-up, which was at least 1 year in 15 participants." I'd be curious to see if it holds up after 10 years. When the edited cells undergo mitosis, the updated gene is replicated too, so the overall ratio of old-DNA to new-DNA cells remains constant over time. I guess follow-up infusions would only be necessary if something about the alteration affects cell health or division rate unexpectedly.