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Pre-Existing Immunity to CRISPR Found in 96% of People in Study
- ajuc 8y agoDoes that mean if we introduce modified enzyme to circumvent this immunity - bacteries could steal it and become much more dangerous?
- emiliobumachar 8y agoIt depends on how we make the enzyme. If it's made without involving life in any way, it's hard to imagine how bacteria would "learn" to make it after finding it. At most, opportunistic bacteria could better parasite people already loaded with enzymes from CRISPR treatment. If we modify harmless bacteria to build the enzyme for us, then sure, the modification could well end up on harmful bacteria.
- grenoire 8y agoThis 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?
- jonwachob91 8y agoPer 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,” "
- wernercd 8y ago> we have all been through multiple infections Does that mean it could be used when young, before the immune system is primed?
- virusduck 8y agoThe 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-self protein bits on the surface of cells, and when non-self is detected, they kill that cell they perceive as infected. There's a bit more nuance than this, but this makes it significantly more difficult to pull off gene editing in a human.
- TheSpiceIsLife 8y agoCould this be a potential cancer therapy?
- mjevans 8y agoI 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.
- deleted 8y ago[deleted]
- virusduck 8y agoIn 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.
- amelius 8y ago
- virusduck 8y agoActual article: https://www.nature.com/articles/s41591-018-0204-6 https://www.nature.com/articles/s41591-018-0204-6 This is perhaps not surprising, but still very disheartening news
- nvahalik 8y agoI 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.
- criddell 8y agoWhen you see a hammer lying around, do you think of the things that could be built or the things that could be destroyed?
- codeulike 8y agoI think "who left that hammer there?"
- dharma1 8y agoHammers don't have unexpected, wide reaching consequences generations down the line, by which time it's too late to do anything about it. Hammers don't also fundamentally change the course of evolution. It's like comparing a slingshot with a nuclear missile
- tomrod 8y agoDepends on how old I am/mature I'm feeling. Presently? Build. 6 years old? Bottle and rock smash time.
- nvahalik 8y agoPersonally, I make a mad dash to it before one of the kiddos decides to smash something with it!
- opportune 8y agoMaybe you could deliver the CRISPR payload through some sort of pathogen-like mechanism such as a virus
- deleted 8y ago[deleted]
- deleted 8y ago[deleted]
- nickelcitymario 8y agoSo 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.
- chongli 8y agoCRISPR holds way more promise than silly fantasies of human genetic enhancement. The most exciting and practical uses for it apply to challenging everyday problems: food, energy, invasive species, biodiversity. Besides, the ethical problems with experimenting on human beings are extremely intractable.
- nserrino 8y agoHow is a CRISPR trial on a terminal patient any different than another experimental medical trial on that same terminal patient?
- whatshisface 8y agoBecause you don't modify the genetics of terminal, living adults, you want to modify the genetics of single-cell healthy zygotes (who will, you hope, later develop into healthy adults).
- mbreese 8y agoSure you do. A lot of the promise of CRISPR therapies were for modifying cells in an adult or child. Using CRISPR/cas9 to “fix” a genetic issue in someone who was already born. For example for adding back a good copy of the gene that causes cistic fibrosis or sickle cell anemia. There were also potential cancer therapies based on the technique. In these cases, the presence of cas9 antibodies is a severe limit to many of the techniques that these companies were working towards.
- jjcm 8y agoCould 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?
- mertd 8y agoThis is discussed in the article. Maybe read before commenting?
- nickles 8y agoThis 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 https://www.biorxiv.org/content/early/2018/04/04/295139 [1] https://twitter.com/GaetanBurgio/status/1057206850213441542 https://twitter.com/GaetanBurgio/status/1057206850213441542
- meowface 8y agoIt's really amazing that humanity is at the stage where we're intentionally evading our own immunity to bacterial components so we can repurpose the components to help ourselves.
- naravara 8y agoWhat if it’s actually just time travelers coming back to code the immunity into us to protect us from the unintended consequences of gene hacking? (This is a joke, in case that needs clarifying)
- kowdermeister 8y agoIt's already like hacking some alien computer in a short amount of time :)
- kitd 8y agoThere's got to be a great scifi story in there somewhere.
- justfor1comment 8y ago
- jf- 8y agoCRISPR Cas9 is present in somewhat varying forms across many (all?) bacteria. I don’t have the quote to hand but I know CRISPR from bacteria that rarely or never come into contact with humans (think extremeophiles like deep sea thermal vent bacteria) doesn’t provoke an immune response, as it’s slightly different in form and novel to the human immune system. This is not a huge setback for CRISPR research. Also you could argue that the title is misleading, as stating that CRISPR evokes an immune response is inaccurate; CRISPR from a bacterium that frequently comes into contact with most humans evokes it, and not all CRISPRs are the same.
- mitchtbaum 8y agoWell, if CRISPR fails it was worth a try anyway. What other potential breakthroughs you got?
- reasonattlm 8y agoImmunity is the standard problem for most vectors for gene therapy. Viral vectors have neutralizing antibodies, liposomes get eaten by macrophages, and so forth. Minimizing this issue to the degree needed for a therapy to work is the subject of a great deal of effort over past decades, and ongoing today. It isn't a solved problem, but there are many incremental approaches that, when combined, can let therapies work well enough given good engineering and good fortune.
- The_rationalist 8y agoWhat about the arguably superior and patent free Cpf1 ? https://en.m.wikipedia.org/wiki/CRISPR/Cpf1 https://en.m.wikipedia.org/wiki/CRISPR/Cpf1
- 88e282102ae2e5b 8y agoCpf1 is patented, it's just that there's no dispute over who owns it.
- The_rationalist 8y agoSorry for the delay, SOURCE please
- plaidfuji 8y agoI see this as more of a reminder of the strength of our immune system than a failure of any particular technology. As a recent post on HN said, fall in love with the problem, not the solution. Whether or not CRISPR works, there’s an enormous community of people who devote their lives to treating genetic disease, which is the underlying problem. At the same time, I’m glad my body has the ability to stop some random bacteria from editing my genome with minimal effort.
- kanzure 8y ago"Exploring protein orthogonality in immune space: a case study with AAV and Cas9 orthologs" https://www.biorxiv.org/content/early/2018/01/10/245985 https://www.biorxiv.org/content/early/2018/01/10/245985
- Uhrheber 8y agoMaybe we're living in a time loop, where the global gene manipulation catastrophe (aka Zombie Apocalypse) has already happened, and we, as the descendants of the survivors, are immune to it.