Hacker News new | past | comments | ask | show | jobs | submit login
Find and Replace: DNA Editing Tool Shows Gene Therapy Promise (nih.gov)
77 points by sciadvance on Jan 24, 2017 | hide | past | favorite | 17 comments



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.wikipedia.org/wiki/Jesse_Gelsinger). It froze gene therapy funding for 10 years. Siddharta Mukerjee has a really good discussion on it in his book, The Gene.

Scaling gene therapy is THE problem of gene therapy. Not editing genes themselves.


(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.


Sounds like they would need to know how to grow massive amounts of these cells in culture for this to be viable. As others have noted here, only about 20% of the cells get the desired fix and many cells die in the process of getting the fix.

Cell culture of human and stem cells is non-trivial and rarely gets done on a large scale. Most of the time you have to grow cells in a petri-dish which in practice means you get very low cell density (number of cells per volume of space it takes to culture the cell i.e. the stacking of the petri dish, the 2D surface they occupy in that dish, how dense the cells like to get within that dish before dying etc.). Ideally you want to grow things to high density in a medium where the cells can out-compete all contaminants. One example is yeast fermentation, the yeast outcompetes everything. Another is e-coli in the lab, where the coli grows faster than most anything in the culture. All of these are liquid suspensions, not on dishes.

In this case, we're talking about a blood disease, so you may be able to grow the cells in liquid culture. You also have easy access to a lot of them (blood is pretty easy to get, in contrast to say, brain). This is where CRISPR is most likely to show results in the clinic in the near future, but there are still lots of hurdles to overcome.


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-existing cells that are mutants at any site. This works because the mutants are "immune" due to lacking the recognition sequence.

Then again, I haven't read a paper on it in awhile now (and the ones posted here seem to be mostly editorials nowadays), so maybe they figured something out.


"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.


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 with the very real risk of death via immune hyper reaction.


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.


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.


From what I read in previous posts here in HN, blindly running find & replace on your code might cause some side effects.


This is the most hyped up biomed topic I have seen in the last 10 years.


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.


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




Guidelines | FAQ | Lists | API | Security | Legal | Apply to YC | Contact

Search: