Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Cells edited using CRISPR–Cas9 injected into a person for the first time

nature.com

Post reply on HN
Print view View original

41–50 of 55 posts

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#41

Post by speeder »

leggomylibro wrote: post #15
dave_sullivan wrote: post #13

Earlier quoted context omitted.

> it would probably make more sense to just knock out the activated oncogene(s) in the patient's cancer I've been wondering about that for the past couple of years, since I heard of CRISPR basically. Who is working on this aspect most seriously right now? Is there any interesting published progress? I understand it will take a while to make real progress, but mostly I'm just curious as an outsider to the industry.

I don't think anyone is; it's still too far out there. I'm sure that there's plenty of research building towards it, but I couldn't name any names. I'm also an outsider to the industry, but CRISPR is actually a simple protocol that doesn't require much advanced equipment, and I've been looking into using it for some home science projects. The problem as I understand it is that right now, CRISPR requires some manual s…

My sister, despite not even having complete her masters yet, is the leading CRISPR-Cas9 person in my country, and was sent to MIT to improve her technique.

You are completely correct, in fact one thing that was notable about it was how much work intensive it is, she was forced to miss lots of family events because she had to go in the lab work on the cells, it requires lots and lots of manual labor.

That said, the stuff IS awesome, after you figure how to get it right, it can get right a lot. (but she did this with animals, where she CAN attempt trial and error until she figures the right reference gene sequence to use to guide the proteins, I dunno how that would work when you are racing against time to save a live patient for example, specially if you want to edit his heart or some other area that is hard to access).

By the way, one of the motivations of MIT new variations of CRISPR (that don't use Cas9) is that Cas9 technique require big needles if you want to work in a living organism, the new ones would allow you to use much smaller needles, that are more practical to stab into a patient... and it is very forward thinking, because people didn't even tried stabbing CRISPR needles into someone yet, it is just that MIT guys realized it would be impractical with Cas9 and decided to invent another technique before actually trying it.

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#42

Post by nonbel »

ihodes wrote: post #33
nonbel wrote: post #14

>"The researchers removed immune cells from the recipient’s blood and then disabled a gene in them using CRISPR–Cas9, which combines a DNA-cutting enzyme with a molecular guide that can be programmed to tell the enzyme precisely where to cut. The disabled gene codes for the protein PD-1, which normally puts the brakes on a cell’s immune response: cancers take advantage of that function to proliferate. Lu’s team then…

It's certainly the former; CRISPR is used to mess with a gene, not kill a population of cells. This isn't what the trial is looking to validate.

>"CRISPR is used to mess with a gene, not kill a population of cells."

Look it up, in every paper where they report on that aspect, the vast majority of the cells die. Also, they detect small numbers of mutants in the control (non-"modified") cells.

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#43

Post by Symmetry »

xorxornop wrote: post #25
qoobaa wrote: post #17

This makes me feel that i.e. looking for bone marrow donors may become obsolete in some cases, if we know the gene sequence responsible for the disease. Instead of looking for donors, it may actually be possible to repair bone marrow cells and inject them back, fixing the problem. Am I missing something here?

Nope, not missing anything. It should also be possible to use it it to reprogram mature cells (such as skin cells) into homeopoetic stem cells in-mass , and simply introduce them into the appropriate site (eg bone marrow, for your example)

Wait, I thought that CRISPR was a matter of gene editing but that stem versus other types of cells was a matter of gene activation? Wouldn't that require different techniques?

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#44

Post by Symmetry »

dghughes wrote: post #9

I think the best (or worst?) part is that CRISPR can be used with a 'gene drive' it keeps the changes active on on-going it's not a one shot thing. GATTACA?

GATTACA just relied on gene analysis (including among a number of blastocycts) but no gene editing. Though I was very annoyed at that movie for implying that people who get diseases just have insufficient willpower.

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#45

Post by nonbel »

ejstronge wrote: post #22
nonbel wrote: post #19

Earlier quoted context omitted.

That seems to be the favorite interpretation. We need to see what data they present that favors it (ie % survival of the treated cells, number of initial cells, % mutants at that location detected in control cells). Also, this is kind of weird, because they say it is non-randomized: Study Design: Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Lab…

I would be surprised if this safety trial were randomized with respect to the CRISPR manipulation. I agree with your assessment of needing more data to believe that the gene editing manipulation was successful. I suspect the randomization relates to the allocation to the experimental arms as described on the reporting page: This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T…

Nice catch, why do you think a safety trial should not use randomized allocation of the treatment (but it does make sense for dose) though?

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#46

Post by avisser »

Symmetry wrote: post #44
dghughes wrote: post #9

I think the best (or worst?) part is that CRISPR can be used with a 'gene drive' it keeps the changes active on on-going it's not a one shot thing. GATTACA?

GATTACA just relied on gene analysis (including among a number of blastocycts) but no gene editing. Though I was very annoyed at that movie for implying that people who get diseases just have insufficient willpower.

> We want to give your child the best possible start. Believe me, we have enough imperfection built in already. Your child doesn't need any more additional burdens. Keep in mind, this child is still you. Simply, the best, of you. You could conceive naturally a thousand times and never get such a result.

I always thought the editing was implied even if it wasn't explicitly called out.

Jerome was different in that he was not edited.

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#47

Post by dekhn »

leggomylibro wrote: post #12

So this title is a bit misleading; something like, "cells edited with CRISPR injected into a person for the first time" would be better. While CRISPR is promising for topological treatments, that's not what happened here. The team took white blood cells out of a patient's body, used CRISPR to knock out a gene which suppresses immune response, then injected those same cells back into the patient, hoping that they woul…

ANy time a person says about human medical processes "more sense to just..." it means you don't understand the complexity of the problem.

We've already seen previous methods of attempting to "knock out" or "Repair" genes with gene therapy; it's an entirely non-trivial problem for a large number of different reasons.

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#48

Post by dekhn »

tropo wrote: post #18
leggomylibro wrote: post #15

Earlier quoted context omitted.

I don't think anyone is; it's still too far out there. I'm sure that there's plenty of research building towards it, but I couldn't name any names. I'm also an outsider to the industry, but CRISPR is actually a simple protocol that doesn't require much advanced equipment, and I've been looking into using it for some home science projects. The problem as I understand it is that right now, CRISPR requires some manual s…

Project idea: The death cap mushroom is really tasty according to people who are now dead. Disable the poison.

you would do that chemically, after collecting the mushroom/while cooking it, because that's easy.

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#49

Post by Symmetry »

avisser wrote: post #46
Symmetry wrote: post #44

Earlier quoted context omitted.

GATTACA just relied on gene analysis (including among a number of blastocycts) but no gene editing. Though I was very annoyed at that movie for implying that people who get diseases just have insufficient willpower.

> We want to give your child the best possible start. Believe me, we have enough imperfection built in already. Your child doesn't need any more additional burdens. Keep in mind, this child is still you. Simply, the best, of you. You could conceive naturally a thousand times and never get such a result. I always thought the editing was implied even if it wasn't explicitly called out. Jerome was different in that he w…

You're right that the text doesn't call it out but I was assuming PGSD[1] which would have the same practical effects and would be less controversial.

[1]https://en.wikipedia.org/wiki/In_vitro_fertilisation#Preimpl...

Re: Cells edited using CRISPR–Cas9 injected into a person for the first time

#50

Post by ihodes »

nonbel wrote: post #42
ihodes wrote: post #33

Earlier quoted context omitted.

It's certainly the former; CRISPR is used to mess with a gene, not kill a population of cells. This isn't what the trial is looking to validate.

>"CRISPR is used to mess with a gene, not kill a population of cells." Look it up, in every paper where they report on that aspect, the vast majority of the cells die. Also, they detect small numbers of mutants in the control (non-"modified") cells.

I haven't read a ton of CRISPR/CAS papers, but I have read the seminal ones, and didn't see that. Mutations in unmodified cells are completely expected, of course, but not mutations in line with where CRISPR is being targeted—I'd hardly believe that to be the case. It looks like the cell perforation (getting CRISPR/CAS into the cells) can certainly affect cell viability, but those numbers have been steadily, rapidly improving. Quick search shows that in 2015, a study found 80% viability post perforation and CRISPR/CAS application (http://advances.sciencemag.org/content/1/7/e1500454.full).
Post reply on HN