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Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

directorsblog.nih.gov

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Re: Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

#11

Post by moh_maya »

danieltillett wrote: post #10
pogba101 wrote: post #9

I really wish I could get the take of an impartial scientist on this. How much is hype vs reality?

I am a scientist and I am impartial if that is good enough :) The major problem is the same as it has been for the last 30 years - delivery. You can make the most amazing molecular machinery for modifying genes, but if you can't get it into a very high percentage of adult cells then it is useless for most treatment purposes. We still don't have any good delivery systems that work on all cell types and doesn't come wi…

This. Completely. Also, I still worry about off-target edits / changes, though that is less of a concern with the technologies available today compared to even 5 years back.

But delivery remains the biggest challenge.

Re: Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

#12

Post by lisivka »

danieltillett wrote: post #10
pogba101 wrote: post #9

I really wish I could get the take of an impartial scientist on this. How much is hype vs reality?

I am a scientist and I am impartial if that is good enough :) The major problem is the same as it has been for the last 30 years - delivery. You can make the most amazing molecular machinery for modifying genes, but if you can't get it into a very high percentage of adult cells then it is useless for most treatment purposes. We still don't have any good delivery systems that work on all cell types and doesn't come wi…

IMHO, in some cases, cells can be converted into stem cells, repaired in lab conditions, and then delivered back into damaged organ or area.

Re: Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

#13

Post by danieltillett »

lisivka wrote: post #12
danieltillett wrote: post #10

Earlier quoted context omitted.

I am a scientist and I am impartial if that is good enough :) The major problem is the same as it has been for the last 30 years - delivery. You can make the most amazing molecular machinery for modifying genes, but if you can't get it into a very high percentage of adult cells then it is useless for most treatment purposes. We still don't have any good delivery systems that work on all cell types and doesn't come wi…

IMHO, in some cases, cells can be converted into stem cells, repaired in lab conditions, and then delivered back into damaged organ or area.

Yes some haematological diseases can be treated this way, but not much else. We really need much better delivery systems that work in all tissue types.

Re: Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

#14

Post by TeMPOraL »

_m8fo wrote: post #8

Is it a false dichotomy for me to say: "we can't even fix the economy; I'm skeptical to think we're going to do any serious modifications to our DNA with positive, well directed results that are absent in shocking negative side effects."? Disclaimer: I know more about the economy to DNA, which is to say, still not very much.

I think economy is harder than biology, for the same reason it's harder than physics - because economy involves thinking actors with conflicting goals, many of whom will happily use their cognitive powers to oppose your fixes to the economy. Biology may be complex, but it's not made of actors smarter than you who will work against you, sometimes just out of spite.

Re: Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

#16

Post by dekhn »

mjfl wrote: post #7
xiphias wrote: post #2

It would be interesting to know how the scaling-up procedure works? Is it similar to scaling up and productionizing a software system? Anyways, I guess the only question is how much time it will take to have mass-scale gene editing on people.

Absolutely not. Scaling is the whole problem with gene therapy. If we could scale it we would have had it in 1999. In that year, a man was injected with lentivirally carried genetic therapy to cause his liver cells to break down ammonia (they weren't before and he couldn't eat certain foods, lived an uncomfortable but livable life). He died due to the immune response. His name was [Jesse Gelsinger]( https://en.wikipe…

(I know the answer, but) Why would the death of a single person from a clinical trial freeze an entire category of funding? Surely, many people die in clinical trials of other types of medicine (caused by the treatment) and that doesn't cause the trials to be shut down. Immunotherapy of cancer wouldn't be a viable treatment if subjected to the same level of regulation as gene therapy.

Re: Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

#17

Post by dekhn »

nonbel wrote: post #3
xiphias wrote: post #2

It would be interesting to know how the scaling-up procedure works? Is it similar to scaling up and productionizing a software system? Anyways, I guess the only question is how much time it will take to have mass-scale gene editing on people.

If you are imagining having something injected into you and your cells being "edited" in situ, I doubt it can happen with this tech. The process is very toxic to cells in every paper that reports that aspect. You will only see them remove the cells, "edit" them in a dish, then inject them back in. I even suspect a major portion of the "editing" is not editing at all, but rather selecting for the small number of pre-e…

"The process is very toxic to cells...." you mean like chemotherapy?

Re: Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

#18

Post by dekhn »

_m8fo wrote: post #8

Is it a false dichotomy for me to say: "we can't even fix the economy; I'm skeptical to think we're going to do any serious modifications to our DNA with positive, well directed results that are absent in shocking negative side effects."? Disclaimer: I know more about the economy to DNA, which is to say, still not very much.

The barriers to treating people with gene therapy are primarily social at this point, not medical or scientific.

Re: Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

#19

Post by nonbel »

dekhn wrote: post #17
nonbel wrote: post #3

Earlier quoted context omitted.

If you are imagining having something injected into you and your cells being "edited" in situ, I doubt it can happen with this tech. The process is very toxic to cells in every paper that reports that aspect. You will only see them remove the cells, "edit" them in a dish, then inject them back in. I even suspect a major portion of the "editing" is not editing at all, but rather selecting for the small number of pre-e…

"The process is very toxic to cells...." you mean like chemotherapy?

Yes, the way CRISPR/Cas9 works, the DNA must be damaged.

However, chemotherapy is not very selective about which cells it damages. Here, the DNA is much more difficult to damage if it is already missing the exact sequence being targeted for "editing", so the targeted cells will die while the mutants divide to take their place.

If I thought specific somatic mutations were good drug targets for cancer, I would be more enthusiastic about CRISPR/Cas9 as a less toxic chemotherapy than a gene-editing therapy.

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