Harvard Researchers CRISPR editing-out apoe4 (from sperm)

[Fiver]

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Harvard Researchers CRISPR editing-out apoe4 (from sperm)

https://www.technologyreview.com/s/6124 ... ing-sperm/

To alter the DNA inside sperm cells, the team is using a clever new version of CRISPR called base editing, developed by another Harvard scientist, David Liu. Instead of breaking open the double helix, base editing can flip a single genetic letter from, say, G to A. One such molecular tweak is enough to turn a the riskiest version of the ApoE gene into the least risky.

“It’s one letter, G to A. You take it from risk to non-risk,” says Neuhausser.

For now, ApoE is a toy example, one to try in the lab to test the technology and its potential. It’s not certain yet whether changing this gene would alter a child’s risk of Alzheimer’s later in life. Despite very strong links to the brain disease, there is no rock-solid proof that ApoE is a cause. “It’s one of the main risk factors for Alzheimer’s, although no one has shown causality,” says Neuhausser. “The point is to show the principle.”

[Fiver]

BTW I'm not sure I agree with the underlined part. I think the proof is pretty rock-solid. And research has shown causality, unless they mean we ought to pick apoe4 into human volunteers to see if they get the disease (which is absurd).

[mike]

One such molecular tweak is enough to turn a the riskiest version of the ApoE gene into the least risky.

I thought the change 4 to 3 was at a different location than the change from 3 to 2, so I would think you would need to do two such tweaks to go from a 4 to a 2... Still, once tested and safe, I would jump at the chance to have my grand kids not have to have an ApoE4...

[Fiver]

Yeah, I think the science writer is getting some details wrong. But clearly they are going to do it, at least up to the doing it in cells part. All sorts of questions.

[mike]

I grew up on Star Trek. Yes, it will happen. I have a grandchild in the works - 50% chance of having one ApoE4. Would like to eliminate that chance for any future ones. But yes, lots of questions. What kinds of changes will be allowed? Just disease prevention? Will the rich get to be smarter and live longer?

[Julie G]

“It’s one letter, G to A. You take it from risk to non-risk,” says Neuhausser.

Pure arrogance. We have no idea what this will do. It's worth remembering, ApoE4 has persisted since the dawn of man. It wouldn't have survived without bestowing some benefits...

[Fiver]

Makes it sounds like a simple global find and replace in a Word document.

All sorts of questions:

If it's worthy of eliminating the gene, does that make it a "disease" gene? that has policy implications.
If it is a "disease" gene is it immoral *not* to eliminate it?
If parents can eliminate the risk, but don't.....interesting conversations.....
If it is eliminated from new generations, how? when? who? the whole GATTACA movie thing.
Does this create sandwich generations of apoE4s with less incentive to "solve" their challenges? The equivalent for older people is gene-therapy to change the genes of million of cells in the brain - a tougher challenge.
If it's good to have the gene around, because it probably does some good for the species, does the gene need to be carried around in living people or is it good enough to have in on a lab shelf or database, just in case?
Is it any different to change a 4/4 to a 4/3? or a 3/4 to a 3/3?
If there are side-effect of the procedure, who pays to care for the patient?
How could insurance companies *not* eventually require apoe genetic testing to get insurance in light of all this?

I'm conflicted. Studies done to date indicate that switching E4 to E3 eliminates AD pathology. And it's already been done, on a limited test basis, for a couple of other diseases. But, gee, it seems like a time-out and a conversation is in order.

But it's pretty clear, one way or another, it's happening.

[Julie G]

Makes it sounds like a simple global find and replace in a Word document.

Exactly!