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The actual study is here. It's a remarkable achievement: https://www.nejm.org/doi/full/10.1056/NEJMoa1815408

No CRISPR/Cas9 was used in this study.

We'll have to wait and see if any of the patients develop hematologic malignancies (blood cancers).

I predict we'll see dozens of papers like this in the next few years. Sickle cell and thalessemias are low hanging fruit.



Would any of this work for auto-immune diseases? Some of them are linked to genetic markers like HLA-B27 and HLA-DR4


Not with this approach. It's easier to add a gene to one cell lineage (in this case, the blood cell forming hematopoietic lineage) than to remove a gene from every single cell in the body.

But there are other strategies in development to help some patients with autoimmune disease. This is one of my favorite papers in that vein: https://www.ncbi.nlm.nih.gov/pubmed/27365313


Do you have to remove a gene from every cell in the body, rather than modify the blood cells so they don’t attack the rest?


Right--see the paper I linked to above for an example of that. Here's a summary article: https://www.cell.com/molecular-therapy-family/molecular-ther...

If you can't access it then shoot me an email at ron gejman at gmail dot com and I'll send you the pdf.


CRISPR has much better targeting than lentiviral gene editing, so it should have much lower rates of cancer too.


The incredibly vast sphere of gene-to-gene interactions is very poorly understood.

Anything changed in the DNA can have completely unforeseen consequences because genes and their products influence expression of other genes.

Which genes does each gene influence? Directly or indirectly? To what extent (strength of up- or downregulation)? Only under specific conditions? Only if 3 other genes are present and not regulated in a different manner?

I have done some computational gene interaction analysis by building regulatory interaction networks in Cytoscape using sequencing and expression data based on specific research [1].

My subjective impression is that messing with genes is little but an unpredictable endeavor at this point. The gamble may pay off but I don't think anyone can honestly tell you something about long-term effects in each individual.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503487/


I think i'd take the gamble over living in an isolation room for my entire life


It doesn't really matter whether you would or would not take the gamble; it depends on whether the FDA would be willing to let you.

(I'm not saying this as some kind of rrrgh-gubmint-bad thing. It's pretty normal for the government to have authority over what gambles are acceptable to offer in what circumstances, and which ones are exploitative and detrimental to even offer; this is the logic behind, for instance, regulations of actual gambling.)


Yes of course, but think about gene therapy for far less intrusive health issues.

If more common and widespread health problems are tackled with gene therapy and we wouldn't know the consequences long term (we really don't) then this aspect becomes far more problematic.

Like you, I would also take the gamble if it's a Hail Mary attempt at surviving or making a somewhat normal life possible. But that's not the point I was trying to tackle.


Not all of it is just targeting the right sites - IIUC the last time we tried gene splicing for this, the splices worked, everything looked great for a little while, but the sites had oncogenes right next to them that got activated by the splicing.

I'm hopeful that this is a panacea for this class of problem the likes of which we rarely see, but I will not be surprised if something tragic happens.


What's your level of experience with this subject?

Where can I learn more about gene therapy as well as CRISPR/Cas9?

Specifically seminal papers?

Where can I learn more about the business aspect of it? Industry, projections, opportunities, etc.

Thanks in advance!


thalassemias. Felt compelled to let you know the correct spelling. I happen to know simply because I know the two Greek words for Thalassocracy.


What's your level of experience with this subject?

Where can I learn more about gene therapy as well as CRISPR/Cas9?

Specifically seminal papers?

Where can I learn more about the business aspect of it? Industry, projections, opportunities, etc.

Thanks in advance!




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