1. Ian Jeffreys @DNAian

    Greg I think EDNA is a great DAC and I share your vision.

    But as an educator I do think your video was a bit misleading when you say I have “ A vial of a human knock out for the human MSTN gene” (The myostatin gene) “You put this in your body and you lose the MSTN gene”. I share your passion for CRISPR technology and have been following the technology very closely since the 2012 Doudna lab Science paper. Yes CRISPR gene editing is powerful but they way it was presented by you, it came off like you could just drink the vial (or put it in your body) and you would have a cure. As you know, delivery of the the guide RNA and CAS9 (and repair template) is a major challenge with CRISPR and with gene therapy in general. On top of that, for some “cures” it would require you to modify the germline cells to cure future progeny. Again, I am sure this will happen in the future, but it will take time and a lot of red tape regulations. There is promise with somatic cell gene modifications and this will happen first before germline editing. CRISPR has potential for metabolic disorders where you only need to repair the gene in a certain tissue (ie liver). I do have hope that some day CRISPR will be used routinely on humans, but it will take time and will be highly regulated.

    The kid and bull (Belgian Blue) have acquired natural mutations in their myostatin gene. Yes, I know they have used CRISPR in mice and dogs to do germline knock outs of myostatin and maybe you should have shown those as examples, but I don’t want the public thinking that doing this would be as easy as swallowing a pill.

    Greg I love your work and what you are doing (I hold EDNA) so please take this as constructive criticism.
    Love Genetics!

    1. Greg Simpson Post author

      Hello Ian,
      I completely understand your point. There are a good many excellent presentations on the subject of CRISPR, and I hope my 7 seconds on the subject encourages people to learn more. In hindsight “…you will here more and more, that is the future…” is not a very clear statement of the current state of the tech, but I assure you, it was not intended to be misleading. Was it incomplete? for certain! Zero argument there.

      The human CRISPR I held up in the vial was a MSTN gene knockout synthesized by and purchased from and delivered to me as a plasmid in bacteria. Another delivery option is to use an Adeno Associated Viruse. AAVs are the safest and easiest ways to get the DNA in cells are gaining popularity in gene therapy. Even though they are the most efficient, they are still far from “one shot, and done.” They are also more costly, and let’s not forget, there’s a whole lot of mussel cells in a human. The bacteria vector is my choice to experiment with even though it’s less efficient because all I need is to feed the bacteria some sugar water and I can “breed up” as much CRISPR as I want. However, even with a swimming pool of the stuff, the issues around getting it past the cell walls do create a serious barrier to “popping a pill” and forgetting it – till you’re big and strong enough that you decide to pop the MSTN Knockin and “undo” the edit.

      So until we have a much better way of getting the CRISPR past the cell wall where it can work its’ magic on our DNA, we are stuck with low efficiency vectors (a plasmid or viral chromosome into whose genome a fragment of foreign DNA is inserted, used to introduce the foreign DNA into a host cell)

      Wait! I wonder if these guys will sell me few trillion of what’s in their test tubes? [Grin]

      1. Ian Jeffreys @DNAian

        Nano machines and optogenetics very powerful indeed! AAV are promising but they can integrate in the genome somewhat randomly and you don’t want it knocking out an essential gene. Bacteria delivery (ie in the form of a probiotic) is very promising. One area where I think CRISPR technology will excel is the designing “targeted antibiotics”. Antibiotics today, for the most part, are non selective and wipe out the bad bacteria and also your good bacteria. Our DNA (our genome) is important, but there is another genome we all have and that is the human microbiome (all of the bacteria and viruses on and in us) that is very important for human health and has diverse roles in human physiology including, obesity, cancer, and even mental health. With CRISPR we can now target specific bacteria that are pathogenic but at the same time leaving behind our good bacteria. Clostridium difficile, or C. diff. comes to mind as this is a serious infection in the hospital setting. We know now that whiter you are sensitive or resistant to C. diff. depends on your microbiome. How would we deliver CRISPR components to patients? Phage (viruses against bacteria) will likely be the answer. Just modify phage to target and kill the pathogenic bacteria.
        Some really exciting times ahead of us!
        btw from the video you can see that the general public is still very skeptical about GMOs, but hopefully with proper education they will embrace the power of genetics. Yes with great power comes great resonsibility and guidelines, regulation, privacy issues will be a very big part of this technology.