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Pre-Existing Immunity to CRISPR Found in 96% of People in Study

xconomy.com

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Re: Pre-Existing Immunity to CRISPR Found in 96% of People in Study

#11

Post by mjevans »

TheSpiceIsLife wrote: post #8
virusduck wrote: post #7

Earlier quoted context omitted.

The enzyme commonly used for gene editing is from a bacteria that is a common human pathogen. Bits of these bacteria (including their Cas9 protein) are recognized as foreign. Unfortunately, when gene-edited cells are expressing the Cas9 protein, bits of every protein in the cell, including Cas9, naturally get processed and presented on the surface of the cell. There are immune cells (T cells) that monitor for non-sel…

Could this be a potential cancer therapy?

I like your silver-lining take on this. It wouldn't be bad low-hanging fruit to look at if someone hasn't already done that study.

Re: Pre-Existing Immunity to CRISPR Found in 96% of People in Study

#13

Post by virusduck »

TheSpiceIsLife wrote: post #8
virusduck wrote: post #7

Earlier quoted context omitted.

The enzyme commonly used for gene editing is from a bacteria that is a common human pathogen. Bits of these bacteria (including their Cas9 protein) are recognized as foreign. Unfortunately, when gene-edited cells are expressing the Cas9 protein, bits of every protein in the cell, including Cas9, naturally get processed and presented on the surface of the cell. There are immune cells (T cells) that monitor for non-sel…

Could this be a potential cancer therapy?

In a way, sure. A major roll of the immune system (especially T cells) is to monitor for unusual cells. Some pre-cancerous cells display unusual markers that are recognized and killed by T cells. Those that evade T cell recognition go on to be a problem.

The major problem is still how do you target cancer cells? If you can find something that makes them unique, say a cell surface receptor, or an unusual metabolic process, there are lots of ways to target them for removal. It's just hard to uniquely identify cancer cells. Right now, most chemotherapy drugs target the phenotype of "fast replication" which really isn't too selective.

Re: Pre-Existing Immunity to CRISPR Found in 96% of People in Study

#14

Post by nickelcitymario »

So to the non-geneticist noobs (like me), is it correct to interpret this finding as suggesting that the promises of CRISPR may be dead in the water?

Does this mean all the hype was nothing more than hype?

Should anyone with investments in CRISPR be seriously looking at dumping their stock?

Should anyone who was holding out on CRISPR to give us super powers / cure disease / etc start drinking copious amounts of alcohol instead?

Despite my tone, I seriously am asking what the implications of this are, because it's not my area of expertise.

Re: Pre-Existing Immunity to CRISPR Found in 96% of People in Study

#16

Post by subcosmos »

TheSpiceIsLife wrote: post #8
virusduck wrote: post #7

Earlier quoted context omitted.

The enzyme commonly used for gene editing is from a bacteria that is a common human pathogen. Bits of these bacteria (including their Cas9 protein) are recognized as foreign. Unfortunately, when gene-edited cells are expressing the Cas9 protein, bits of every protein in the cell, including Cas9, naturally get processed and presented on the surface of the cell. There are immune cells (T cells) that monitor for non-sel…

Could this be a potential cancer therapy?

My thoughts exactly! Here's how it might work :

Get a construct into the cell that is only transcribed if specific pathways are overly active, effectively testing that cells "cancer status". This is the hard part.....

Then have it translate something pathogenic-looking that gets presented on the surface.

So now the question is, how do you design some kind of promoter sequence that looks for, say, tp53 mutations or something similar?

Re: Pre-Existing Immunity to CRISPR Found in 96% of People in Study

#17

Post by nvahalik »

virusduck wrote: post #4

Actual article: https://www.nature.com/articles/s41591-018-0204-6 This is perhaps not surprising, but still very disheartening news

I could be wrong, but this seems like a blessing in disguise. Maybe I'm just totally ignorant about CRISPR but from what I have read, it seems like this is totally wild-west/uncharted territory. This seems like one of those technologies that could have massive unintended consequences. Perhaps this is a _good_ thing rather than a bad thing.

Re: Pre-Existing Immunity to CRISPR Found in 96% of People in Study

#18

Post by nickles »

This will likely not be an impediment to treatments based on CRISPR. The study has been available in preprint form for ~6 months on biorxiv [0]. At least some of the companies researching CRISPR were aware of this issue at the time the paper was released. It has since been mitigated, as specified at the bottom of the article. From Gaetan Burgio's tweets:

"Published now in @NatureMedicine on #CRISPR & Immunity to SpCas9. 6 months has past since the preprint was online & it is a long time in the CRISPR field. Since then additional work showed how to circumvented this by modifying Cas9 protein or using Cas9 orthologs. So No panic !" [1]

[0] https://www.biorxiv.org/content/early/2018/04/04/295139

[1] https://twitter.com/GaetanBurgio/status/1057206850213441542

Re: Pre-Existing Immunity to CRISPR Found in 96% of People in Study

#19

Post by wernercd »

jonwachob91 wrote: post #6
grenoire wrote: post #3

This is very interesting, is it maybe that CRISPR resembles attacks we faced from viruses and the likes during our evolution as a species, that we have such high rates of immunity to it?

Per the article > "Michael Schmueck-Henneresse of Charité University Medicine Berlin, who led today’s study, said that he was initially surprised by the 96% finding. “But it made sense because the Streptococcus pyogenes bacterium is one of the most common causes for bacterial infections in humans and we have all been through multiple infections and potentially even been colonized by it,” "

> we have all been through multiple infections

Does that mean it could be used when young, before the immune system is primed?

Re: Pre-Existing Immunity to CRISPR Found in 96% of People in Study

#20

Post by mertd »

jjcm wrote: post #15

Could we not just use immunosuppressants to give the crispr editing enough time to spread? Once the genes are edited, purging the CRISPR delivery mechanisms from the system should be fine, correct?

This is discussed in the article. Maybe read before commenting?
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