Targeted in vivo gene integration of a secretion-enabled GLP-1 receptor agonist reverses diet-induced non-genetic obesity and pre-diabetes | Communications Medicine
www.nature.com
In vivo genome editing offers a long-term therapeutic approach for monogenic diseases by directly modifying genetic sequences. However, its application to non-monogenic, noncommunicable diseases, which are the leading causes of global mortality, remains limited due to the lack of well-defined genetic targets. We developed an in vivo genome-editing approach to introduce a gene encoding the glucagon-like peptide-1 (GLP-1) receptor agonist Exendin-4, modified with a secretion signal peptide. Mice with obesity and pre-diabetic conditions received a single administration of genome editing. Blood Exendin-4 levels, food intake, body weight, and metabolic parameters were monitored over several months. Here we show that in vivo genome editing enables sustained Exendin-4 secretion from liver cells, leading to prolonged elevation of Exendin-4 levels in the bloodstream. Treated mice exhibited reduced food intake, attenuated weight gain, and improved glucose metabolism and insulin sensitivity without detectable adverse effects. This study demonstrates that a single administration of genome editing can achieve sustained therapeutic peptide secretion, providing a potential strategy for treating complex diseases without defined genetic causes. Hirose et al. demonstrate a genome editing-based strategy to treat obesity and pre-diabetes, complex diseases without a defined genetic cause. A single in vivo knock-in of a secretion-engineered Exendin-4 gene into the liver enables sustained peptide release, reducing body weight and improving glucose metabolism in mice. Many diseases, such as diabetes and obesity, are not caused by a single change in a person’s DNA so are difficult to treat with regular gene therapy, a treatment type that modifies DNA. In this study, we used genome editing, a tool that makes precise and lasting changes to DNA. We used it to help the body produce and release a beneficial molecule called Exendin-4, which controls appetite and blood sugar. In mice, just one treatment led to long-term improvements in weight and blood sugar, without noticeable side effects. This study suggests that genome editing could be used to create lasting treatments for complex diseases, potentially reducing the need for frequent medication.
    • apotheotic (she/her)@beehaw.orgEnglish
      26·
      17 days ago

      Dude fuck this attitude. I’ve been trying to eat properly for actual years. I try to eat fewer carbs, I count my calories, and do my damnedest to stay in a caloric deficit. I work out frequently and hydrate well. I take a probiotic to ensure my gut microbiome is going to be on its best behaviour.

      And then my body screams at me that I am hungry. And on the first day of this, I can mind over matter. On the second day, it is more difficult, but I can just about keep it up. On the nth day it makes me feel sick with how hungry my body is telling me I am. I eat, and I go over calorie budget. My mindset spirals. I end up 3 weeks down the line and my weight is right back where it started.

      I want to make the change. I’m fucking trying. It is not as simple as people “doing absolutely anything but eating properly”.

      • Cort@lemmy.worldEnglish
        10·
        17 days ago

        And all that doesn’t even touch on modern producers purposely designing their food products to be literally addictive.

      • metaStatic@kbin.earth
        4·
        16 days ago

        you’re being sabotaged by a century of misinformation and food science designed to make you buy more. you end up feeling hungry because you’re not getting what you need from whatever you’re eating. The calories don’t mean shit, you’re not a combustion engine, you need nutrients and the rest literally takes care of itself.

        A low carb whole food diet would be more than enough to see vast improvements but if you can get 30 days of carnivore under your belt your joints will tell you immediately if what you just ate was really food.

        the goal is to be healthy and being a healthy weight is just a side effect.

          • metaStatic@kbin.earth
            2·
            16 days ago

            illness isn’t caused by a lack of medication … it really is as simple as stop doing the thing that harms you.

            • apotheotic (she/her)@beehaw.orgEnglish
              4·
              16 days ago

              It really, truthfully, is not. I never once said that a lack of medication is the thing stopping me from losing weight, so idk why you’re bringing that up, but “just stop eating in an unhealthy way” is a simple sentence but far more complex in practice.

              However, we clearly don’t see eye to eye on this so I’m just going to disengage.

      • Demdaru@lemmy.worldEnglish
        2·
        16 days ago

        First of all, damn.

        Second of all, try drinking water whenever hungry, or chewing gum. It may help. You already got so far, I even slightly jealous ^^’

    • Safeguard@beehaw.orgEnglish
      4·
      17 days ago

      It’s not that simple.

      Good food is expensive and sometimes it looks like good food but still is full of all kinds of shit. Hunger generating chemicals making you eat more for instance.

      I’d love for the FDA to start actually giving a damn instead of people having to be pay to get fat and then pay to get thin.

    • Kowowow@lemmy.caEnglish
      2·
      17 days ago

      The problem is in the moment it can seem like you are doing alright, I almost went and got a slushie with icecream mixed in after I had forgotten I already had a bowl of icecream

  • Lugh@futurology.todayOPMEnglish
    13·
    17 days ago

    Although gene editing techniques are patentable in some countries, I wonder if this could be much cheaper than the monthly weight loss shots, which can be very expensive in some countries.

    In the future will medical tourism for gene editing be a thing? Maybe the same clinics that offer hair restoration, botox and plastic surgery today will have it as an option.

    • Alaik@lemmy.zipEnglish
      2·
      16 days ago

      Gene editing treatments in general are prohibitively expensive (At least in the US). Casgevy cures sickle cell and beta-thallasemia but I want to say it costs $300,000? For the one dose.

      You’d think insurance would jump on that given how much ER visits are, and the prevalence of ER visits in that patient demographic though.