Posted on 05/30/2023 1:22:29 PM PDT by Red Badger
This version of CRISPR doesn’t actually change DNA.
A biotech startup has successfully lowered the cholesterol levels of monkeys using a version of CRISPR that doesn’t permanently alter DNA — suggesting a safer way to take advantage of the groundbreaking technology.
The challenge: Most genes are instruction manuals for making proteins. Those proteins dictate what your cells look like and do, trigger or stop chemical reactions, and influence almost everything else about your body.
Using CRISPR, researchers can edit genes to change these proteins — a CRISPR treatment for sickle cell anemia, for example, corrects a genetic mutation that causes red blood cells to produce irregularly shaped hemoglobin proteins.
CRISPR sometimes edits genes in places it’s not supposed to, though, and those off-target edits can create new problems. Because CRISPR alters DNA itself, the mistakes are usually irreversible, too.
Tune targets epigenetic marks to control gene expression, rather than editing genes themselves.
Epigenetic editing: Nearly every cell in your body contains all of your genes, but because you don’t need every cell to make every possible protein all the time, your body uses chemical compounds called “epigenetic marks” to dictate which genes in a cell are on (or “expressed”) and which aren’t. That’s what makes a heart cell different from a brain cell.
Tune Therapeutics is developing a CRISPR-based platform, called TEMPO, that targets these epigenetic marks to control gene expression, rather than editing the genes themselves. The idea is that this will allow them to influence the proteins that play a pivotal role in our health, without the risk of permanent off-target effects.
What’s new? Tune’s first major test for TEMPO is the PCSK9 gene. Reducing the expression of this gene or blocking its effect lowers LDL (“bad”) cholesterol in people, but the only FDA-approved PCSK9 inhibitor drugs are injections that must be administered regularly, are expensive, and can have side effects.
Biotech startup Verve Therapeutics is using a CRISPR-based therapy, called “base editing,” to permanently turn off the PCSK9 gene by swapping out a single letter of DNA. In monkeys, it slashed LDL-C levels by 70% in two weeks, and the effect appeared to last indefinitely — suggesting it could be a lifetime cure for high cholesterol.
Verve is now running a human clinical trial in New Zealand and the UK, but it has had trouble getting FDA approval to start it in the US, in part because of concerns about potential off-target edits.
Tune is hoping to achieve a similar effect on LDL without permanently altering DNA.
After successful tests in rodents, Tune researchers administered a single dose of their TEMPO treatment to three monkeys intravenously. After 120 days, the levels of LDL-C in the monkeys’ blood had fallen by 56%.
According to Tune, this is the first example of anyone successfully editing the epigenome of a non-human primate.
“This Tune data looks beautiful,” David Segal, a gene-editing researcher at UC Davis, who was not involved in the study, told STAT News. “It does really look like they were able to silence that gene in a very long-term way and they were able to see clinical benefits from that.”
The treatment could be a one-and-done alternative to costly PCSK9 inhibitors.
Looking ahead: Tune’s monkey study is ongoing, and while it’s possible the changes in the animals’ protein levels could be permanent, they also might not be.
“There might be transcription factors or other forces that will try to counteract the kinds of changes we make,” Segal said of epigenetic editing.
If the effect does seem to be long-lasting, the treatment could be a one-and-done alternative to costly PCSK9 inhibitors and might have an easier time getting approval than permanent gene editing. That’s if Tune decides to pursue clinical trials — it’s possible the company might first use the technique to target a disease for which there isn’t already a treatment available first.
“This data is highly encouraging for the field, as it presents a broad proof-of-concept for liver-directed epi-editing and attests to the potential for genetic tuning to unlock common disease and regenerative medicine,” said CEO Matt Kane.
Great news for monkeys.
So basically the key is to fry the bananas?
She can start eating BBQ, drinking whisky, and smoking cigars again.
Who is to say that high cholesterol is a bad thing? My doctor tells me such and such, I ignore him. He gives me pills, I throw them away. I live on. BP is normal, no heart problems... made it to 70, would like to see 80 but that is not in my hands.
CRISPR tool? Is that more like a circular saw or a chain saw? And how exactly does one use it to slash one’s cholesterol?
Unbelievably stupid, but at least they are arrogant too. The body makes cholesterol and it is essential to life. High levels of cholesterol are associated with longer lifespans. Low levels are are correlated to shorter lifespans.
The real enemy is oxidized cholesterol, which is untouched by these treatments.
“tool” is a Home Depot-style, friendly-sounding euphemism for the safety-profile-absent gene-manipulation therapy some (atheist) people are jonesing to make part of every person’s sci-fi hellscape life.
Any thought about what you’ve posted here?
In the absence of dietary cholesterol, your body will simply make its own. The body NEEDS cholesterol to function.
You can have all the steaks and eat all the eggs and butter you want so long as you eat healthy overall and stay away from the hydrogenated vegetable oils and added sugars (which is in almost all supermarket processed foods).
I've been eating three eggs fried in butter for decades and still have normal cholesterol levels. Sometimes I'll whip up a plate of chicken livers, because I like my chicken livers.
“This version of CRISPR doesn’t actually change DNA.”
Nonsense. The whole point of CRISPR is to change DNA.
“My doctor tells me such and such, I ignore him. He gives me pills, I throw them away.”
Impressive. Why do you go to him?
I wonder if this could be used to “temporarily” knock-out human GDF-8 expression... That could be fun. Better and safer than PEDs...
Ah. Gotta have one then— not!
I’d rather be far than having CRISPR running around doing who knows what in my body.
That's the only thing keeping the remaining Rolling Stones alive.
maybe cut back on all the fried grease and it would prolly do wonders
ISWYDT....................
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