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Researchers Use CRISPR To Repair Genetic Defect That Causes Blindness (dispatchtribunal.com)

Posted by timothy on from the ok-now-stop-lettuce-from-wilting dept.

hypnosec writes: In what has been claimed to be the first use of gene editing technique CRISPR for replacement of a defective gene associated with a sensory disease, researchers have repaired a genetic defect that causes blindness. The research that led to successful editing of defective genes responsible for retinitis pigmentosa (RP) – an inherited condition that causes the retina to degrade and leads to blindness in at least 1.5 million cases worldwide – was carried out using stem cells derived from a patient's tissue. Published in Scientific Reports, the study paves the way for using CRIPSR therapeutically to treat eye diseases.

46 comments

  1. recast the last sentence by Anonymous Coward · · Score: 0, Interesting

    "...the study paves the way for using CRISPR therapeutically to treat eye disease."

    needs to read "...the study paves the way for using CRISPR therapeutically to treat all diseases and transform the human species."

  2. Side Effects by eric31415927 · · Score: 1, Troll

    Curing blindness sounds admirable - but at what cost?
    Don't forget the unseen side effects!
    The first Google hit on CRISPR side effects is:
    http://phys.org/news/2015-10-c...

    1. Re:Side Effects by Applehu+Akbar · · Score: 4, Insightful

      The whole point of using GMO technology in an application like this is the 'exceptional specificity' cited in the article.

      "The primary advantage of CRISPR over previous technologies is the ability to use a genetic scalpel rather than a sledgehammer," said Charles Gersbach, associate professor of biomedical engineering at Duke University.

    2. Re:Side Effects by Anonymous Coward · · Score: 0

      Becoming a mutant abomination with superpowers, at which point your destiny is set.

    3. Re:Side Effects by Immerman · · Score: 3, Interesting

      I think you're both right. CRISPR allows for extremely precise gene editing, which is great. (though the wording leaves me unclear on whether they can sometimes cause unintended edits as well - that could be a real problem)

      The problem though, is that we very rarely understand everything those gene edits will do. Very often making a small and specific change in one area may cause a host of unintended side effects as the chain of causality cascades through the many feedback loops of the organism. Maybe you just edited a gene to increase the production of protein X that has some beneficial effect. Well, that means you necessarily reduce the production of at least some other proteins dependent on the same raw materials and production equipment, and that will have its own consequences. And of course there's the direct effect of elevated protein X on the bodies systems, but that part is probably relatively well researched.

      And of course there's also the risk of major and direct unintended consequences. From what I've read we're barely beginning to scratch the surface of understanding how DNA does its thing, but it potentially puts to shame the most convoluted and obscure spaghetti-code ever written by man. There's a very real chance that what looks to be a simple gene to code for X also interacts with other apparently unrelated DNA to do something completely unforseen. Now, if that causes the individual to die horribly then, well, sucks to be the guy to discovers that firsthand, but not really a big problem. What is a big problem is the edit that has only minor obvious effects, or even individually beneficial ones, but also causes long-term environmental issues. Because that's going to inevitably spread through the population, and we'll all have to deal with the consequences. That's more of an issue for our edited food stock contaminating it's wild relatives, but you could imagine things that would have dire effects within the human population as well. To be silly, say we modified a gene that tended to make its carriers far more attractive to the opposite sex, but also caused a serious drop in intelligence.

      --
      --- Most topics have many sides worth arguing, allow me to take one opposite you.
    4. Re:Side Effects by Anonymous Coward · · Score: 0

      Huh? So splicing should use lesser-specificity technology like zinc fingers when CRISPR has shown provably better results? Even with the ongoing patent wars over CRISPR, if you honestly think Sangamo et. al. are going to win over big pharma then I've got a bridge to sell you.

      Here, I'll even do your homework for you, you clueless fucking dipshit:
      Compare this http://www.ncbi.nlm.nih.gov/pu... to this http://www.genecopoeia.com/res... and tell me any problems with CRISPR are worse than ZNF.

    5. Re:Side Effects by Applehu+Akbar · · Score: 1

      All of which side effects are much worse when we fire the hybridization shotgun, mixing and matching many genes at once. Which is why we have never been able to apply this traditional technique to human diseases of the type referenced here. When we hybridize plants we can just toss out the culls. But with genetic engineering, we have a whole new class of disease treatments we never had before.

    6. Re:Side Effects by cheater512 · · Score: 4, Insightful

      How can there be side effects if the only modification is changing a specific already damaged gene back to it's known healthy setting?

      If you are just stabbing around changing random stuff sure there will be random consequences.
      But if you can change specific genes and you know what the damaged state and the healthy states are, you are good to go.

    7. Re:Side Effects by Anonymous Coward · · Score: 0

      Sounds like the potential side effects are largely unknown, probably due to this tech being quite new.

      I am sure the early-adopters can tell us all about the side effects, after driving themselves to work since they can see now.

      Just wait. In five years John Church is going to use this tech to cure aging. Things are about to get awesome!

    8. Re:Side Effects by jedidiah · · Score: 2

      Also, this is a very limited edit. It's not something that is meant to be grown across the surface of the entire planet and released into the wild. It really is quite "surgical" when compared to other forms of "GMO".

      --
      A Pirate and a Puritan look the same on a balance sheet.
    9. Re:Side Effects by Anonymous Coward · · Score: 1

      There are six reading frames to DNA. Changing a sequence of DNA to fix the ability to make one protein, can potentially mess up things that were working properly in the other 5 frames. It is unlikely though, and if we sequence the genomes of patients before applying therapy, mostly avoidable.

    10. Re: Side Effects by Anonymous Coward · · Score: 0

      Or what? Seriously, why is this any different from any other new technology? Of course there will be failures. If that were impossible, there'd be no experiments. Maybe if you drop more f-bombs you can veto the whole thing.

    11. Re:Side Effects by Anonymous Coward · · Score: 0

      "The problem though, is that we very rarely understand everything those gene edits will do. Very often making a small and specific change in one area may cause a host of unintended side effects"

      Uhh, just FYI, we repair these damaged genes by comparing to KNOWN HEALTHY CONFIGURATIONS.

      Please, inform me how known good configurations are bad for us.

    12. Re:Side Effects by Anonymous Coward · · Score: 0

      To be silly, say we modified a gene that tended to make its carriers far more attractive to the opposite sex, but also caused a serious drop in intelligence.

      Sounds like a Brave New World to me!

    13. Re:Side Effects by TechyImmigrant · · Score: 1

      Curing blindness sounds admirable - but at what cost?
      Don't forget the unseen side effects!
      The first Google hit on CRISPR side effects is:
      http://phys.org/news/2015-10-c...

      Without a suitable blindness cure, the side effects will remain literally unseen.

      --
      I should use this sig to advertise my book ISBN-13 : 978-1501515132.
    14. Re:Side Effects by Mal-2 · · Score: 2

      If the edits are localized (performed in vitro, then the cells re-implanted where they belong), the edits won't make it into the germ line. They won't with females regardless.

      --
      How is the Riemann zeta function like Trump rallies? Both have an endless number of trivial zeros.
    15. Re:Side Effects by Pharmboy · · Score: 3, Informative

      I have a friend with Friedrich's Ataxia, and CRISPR is one of the silver bullets she's praying for. FA cripples then kills you: wheel chair by 25, dead by 40 is often the case (it hardens the heart so it can't pump). While CRISPR has some unknowns and risks, having FA is a certainty. FA affects a single gene pair, so if you can replace either side of that gene, you have solved the problem, the mitochondria will start producing frataxin again, and the nerves will stop being slowly destroyed.

      There are no treatments and since it is so rare (1 in 50,000 have it in the US, 1 in 30k in Europe, almost no one in Africa or Asia), few are investing in finding a cure or treatment. FA isn't the only orphan disorder like this. So yes, I'm quite happy to see CRISPR move forward.

      --
      Tequila: It's not just for breakfast anymore!
    16. Re:Side Effects by quantaman · · Score: 3, Interesting

      How can there be side effects if the only modification is changing a specific already damaged gene back to it's known healthy setting?

      If you are just stabbing around changing random stuff sure there will be random consequences.
      But if you can change specific genes and you know what the damaged state and the healthy states are, you are good to go.

      It's a lot better but I don't think it's risk free. Consider a bad variant A and the good variant B.

      B may have also had a developmental role. Only adding B as an adult and missing out on the developmental aspects might mean B functions improperly and causes bad things to happen.

      Also the body may have adapted to A, for instance A is supposed to generate some hormone X and because A generates a crappy version of X your body is hypersensitive to X. Swapping in B and getting the right version of X means your hyper-sensitive body is suddenly overwhelmed by the effects of X and bad things happen.

      Now CRISPR is awesome and revolutionary, but the body is really really complex, and it's hard to do something to a really complex system without having some sort of side effect.

      --
      I stole this Sig
    17. Re:Side Effects by sabbede · · Score: 1

      Don't worry, manufacturers of walking sticks will do fine - there are still plenty of other ways to go blind.

    18. Re:Side Effects by nospam007 · · Score: 1

      "Curing blindness sounds admirable - but at what cost?
      Don't forget the unseen side effects!"

      Since they're blind, all the side effects are unseen.

    19. Re:Side Effects by nospam007 · · Score: 1

      "t's not something that is meant to be grown across the surface of the entire planet and released into the wild."

      Exactly! We can't have all the blind seeing again, their one-eyed king objects to that.

    20. Re:Side Effects by Anonymous Coward · · Score: 0

      but the body is really really complex, and it's hard to do something to a really complex system without having some sort of side effect

      Sure, but how is this different from any other medical treatment? We have no idea what most of the specific off-target effects of conventional pharmaceuticals (or any other internal therapy - that includes you, herbalists) are on humans at a molecular level, just a list of possible side effects, most of which are completely unrelated to the ailment being treated.

    21. Re:Side Effects by quantaman · · Score: 1

      but the body is really really complex, and it's hard to do something to a really complex system without having some sort of side effect

      Sure, but how is this different from any other medical treatment? We have no idea what most of the specific off-target effects of conventional pharmaceuticals (or any other internal therapy - that includes you, herbalists) are on humans at a molecular level, just a list of possible side effects, most of which are completely unrelated to the ailment being treated.

      All I'm saying is that CRISPR doesn't magically eliminate all sideeffects.

      --
      I stole this Sig
    22. Re:Side Effects by Anonymous Coward · · Score: 0

      "Hey, we've got this known good configuration for resistance to malaria!"
      "Awesome! Overwrite every copy that doesn't provide resistance!"
      "....Damn, everybody has sickle cell anemia now."

      Not that I'm opposed to the tech in any way, but you asked.

    23. Re:Side Effects by tibit · · Score: 1

      This is true, but it relates to GMO concerns, not to fixing mutations that cause genetic diseases. In generic diseases, we know exactly what's broken, and we know that fixing it won't break anything either: after all, the rest of us, who don't suffer from the mutation, have the "fix" already!

      --
      A successful API design takes a mixture of software design and pedagogy.
    24. Re:Side Effects by jbengt · · Score: 1

      I, for one, welcome our new naked mole rat visionary overlords.

    25. Re:Side Effects by Immerman · · Score: 1

      True. There still may be unexpected side effects, but so long as they are limited to an individual willing to take the risk, I say pursue it. I think that's actually the reasonable and responsible approach to genetic engineering our own germ line.

      And hopefully we'll understand things a lot better before we decide to proactively cure all our future descendants. After all that's not any more difficult in principle, and absolutely seems to be a reasonable and responsible thing to do, so long as we're actually as competent about it as we think we are. Even in the case of the inevitable mistake, if it's a real problem we can probably detect it within a generation and correct the damage. At worst we introduce a new genetic disease that future generations will need to deal with. Honestly, in a lot of ways editing humans is probably a lot safer than editing most other species - we propagate slowly, report problems, and are already the ultimate invasive species.

      Provided we apply the changes on a small scale, and don't decide to do the efficient thing and release an invisible pandemic to "cure humanity of X". At least not until we're actually as competent as we imagine. I worry though at the lackadaisical attitude some researchers appear to have with regard to making sure their gene-editing viruses don't get into the wild. I recall one fellow giving a TED talk who dismissed fears of his brain-cell modifying virus escaping by saying there was nothing to worry about - he used a harmless, almost symptomless virus. Talk about missing the point! if his infectious gene-editor rode out into the world in one of his test subjects, there could be millions of people walking around the world today with photosensitive brain cells, and there's no telling what long term effects of chloroplast production on those cells might be. What's the effect on a developing embryo?

      I don't know how related to CRISPR that is, but it's the kind of thing I worry about when people start modifying human DNA.

      --
      --- Most topics have many sides worth arguing, allow me to take one opposite you.
    26. Re:Side Effects by Immerman · · Score: 1

      So long as you're able to *only* edit the intended gene with 100% accuracy, you're probably right. It sounds like that might be under debate.

      And assuming that starting out with the "bad" gene didn't modify your epigenome in some way that alters the way the "good" gene gets expressed.

      --
      --- Most topics have many sides worth arguing, allow me to take one opposite you.
    27. Re:Side Effects by tibit · · Score: 1

      Good points!

      --
      A successful API design takes a mixture of software design and pedagogy.
  3. Methods by Anonymous Coward · · Score: 0

    Write a real methods section next time. It is impossible to tell what went on from that, rendering this report worthless other than as a propaganda tool.

  4. CRISPR or CRIPSR by Anonymous Coward · · Score: 0

    Is it CRISPR or CRIPSR? The summary offers both.

  5. The article you reference does not demonstrate any by tlambert · · Score: 4, Insightful

    The article you reference does not demonstrate any side effects.

    However, it is a valid concern, in that in vitro CRISPR/CAS9 and CRISPR/CPF1 edits has historically hit identical palindromic sequences that happened to be outside the target edit area, since the palindromes in question are only 24 or so base pairs in length. You have to expect that there will be other instances elsewhere in the genome.

    If you read the article, the experiment was conducted on pluripotent stem cells created from skin cells taken from the patient, and done in vitro.

    The eventual hope in this case is implantation of the in vitro stem cells in order to correct the defect.

    This means that any side effects can be avoid by separating the edited cells into individual cells, and then culturing each batch to the point some of the batch can be taken and fully sequenced to verify that the only change in the gene sequences relative to the (fully sequenced) parent organisms genome, is the target gene sequence alone. This would be done before implantation, which would guarantee that the gene sequence causing the disease was the only one impacted by the therapy.

    Practically speaking, we have AAVV/AAV-2 techniques -- utilizing Adeno-associated virus vectors, in other words -- that tend to be much more accurate. This is the type of vector that was utilized by the CEO of BioViva, Elizabeth "Liz" Parrish:

    https://www.youtube.com/watch?...

  6. Re:Can a similar technique cure micropenis? by Anonymous Coward · · Score: 0

    Yes witeboi, they can cure your phalitis pigmentosa.

  7. Really? In an adult?? by sabbede · · Score: 0

    That is... so cool. I thought it was essentially too late for alterations to an adult's DNA to have much effect, but I suppose that depends on what you're changing.

  8. Bad for Individual, Good for Community by Anonymous Coward · · Score: 0

    Many disease-causing mutations are beneficial in one copy, problematic with two. The gene for sickle cell anaemia gives heterozygous carriers immunity to malaria, for instance. Ashkenazi have an intelligence-enhancing gene which can also lead to horrific paralysis and death (this one is unusual in that its autosomal dominant, the bad effects are brought on by stress or just by old age, sucks to be smart but also to be watching for the moment your hands start to shake). Point is that gene editing is going to reduce population diversity and will weaken the species even as it strengthens individuals. We should be coming down hard on this stuff in agriculture, or a hundred years from now there will be no cows. To cure eg cystic fibrosis, then yes, I would allow limited use but encourage governments to be very very careful.

  9. Re:The article you reference does not demonstrate by Anonymous Coward · · Score: 0

    CRISPR doesn't target palindromic sequences. It's only hard requirement is that an NGG (for Cas9) be downstream of the target site. Further, the length of the guide sequence (20bp) is sufficient that it will typically hit a unique target. Specificity can be increased by shortening the guide (18bp still works) and by using Cas9 bearing mutations that increase specificity. We're not there yet, but we're really close to actually being able to reliably generate unique edits at any unique sequence in the genome.

  10. Re:The article you reference does not demonstrate by T.E.D. · · Score: 1

    However, it is a valid concern, in that in vitro CRISPR/CAS9 and CRISPR/CPF1 edits has historically hit identical palindromic sequences that happened to be outside the target edit area, since the palindromes in question are only 24 or so base pairs in length. You have to expect that there will be other instances elsewhere in the genome.

    I guess they need to use a larger CRC.

  11. Re:The article you reference does not demonstrate by tlambert · · Score: 1

    Sorry, but the length guide is *not* sufficient.

    While it's more specific than sequence homology predicts, it's less specific than the laser focus it's portrayed as having.

    I understand the need to portray it as being as close to perfect as possible to preserve funding (and the research *should* be funded!), right now, the best method we have of ensuring that off-target mutations do not occur is via post-sequencing.

    See these papers regarding "Dammit, I missed!":

    New Sequencing Methods Reveal Off-Target Effects of CRISPR/Cas9
    https://www.genomeweb.com/sequ...

    Unbiased detection of off-target cleavage by CRISPR-Cas9 and TALENs using integrase-defective lentiviral vectors
    http://www.nature.com/nbt/jour...

    Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases
    http://www.ncbi.nlm.nih.gov/pm...

    CRISPR-Cas9 Specificity: Taming Off-target Mutagenesis
    http://www.genecopoeia.com/res...

    Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells
    http://www.nature.com/nmeth/jo...

    Quantifying on- and off-target genome editing
    http://www.cell.com/trends/bio...

    CRISPR/Cas9 Guide
    https://www.addgene.org/CRISPR...
    Salient quote: "The randomness of NHEJ-mediated DSB repair has important practical implications, because a population of cells expressing Cas9 and a gRNA will result in a diverse array of mutations (for more information, jump to Plan Your Experiment). In most cases, NHEJ gives rise to small InDels in the target DNA which result in in-frame amino acid deletions, insertions, or frameshift mutations leading to premature stop codons within the open reading frame (ORF) of the targeted gene. Ideally, the end result is a loss-of-function mutation within the targeted gene; however, the “strength” of the knock-out phenotype for a given mutant cell is ultimately determined by the amount of residual gene function."

    P.S.: And you know as well as I do that the 'P' in "CRISPR" stands for "Palindromic".

  12. Testing by AaryaPatil · · Score: 1

    Nice article

  13. Testing by Anonymous Coward · · Score: 0

    Nice

  14. Testing by Anonymous Coward · · Score: 0

    Nice article

  15. Interesting by AaryaPatil · · Score: 1

    Interesting

  16. hello by Anonymous Coward · · Score: 0

    Hello