Duchenne’s Muscular Dystrophy, or DMD, has been in the news a lot recently. It’s the most common form of muscular dystrophy and was most recently featured in the Right to Try fight. The FDA also approved the first treatment of DMD’s symptoms in 2017, but a new paper published in Science points to a possible treatment of the root cause of the disorder. Scientists used a system-wide application of CRISPR to efficiently restore dystrophin expression in four dogs, a result that “exceeded [the lead author’s] most optimistic expectations.” There’s a ton of hurdles this treatment would have to pass to be a real therapy in humans, but this could be huge for DMD patients. Also, hey, it’s Labor Day weekend, maybe consider donating to the Muscular Dystrophy Association for Jerry’s Kids.
Not being concerned with pesky ethics concerns, China is pulling ahead in applying genetic editing technology towards therapeutic uses. Not content with being the first to edit monkeys, non-viable embryos, or sticking the first edited cells into a live human, a recent study showed Chinese researchers were able to fix a disease-causing mutation in viable embryos. They used base editing, which is slightly different from Crispr editing (easy-to-digest visual here), to replace the gene which causes Marfan Syndrome. The disease is typically incurable, so there’s obviously some appeal for pushing science’s boundaries for such positive results. Attitudes towards embryo editing may be changing in western nations, but don’t expect base editing to be used therapeutically for some time still.
Two studies released this week looked at the tumor-suppressing gene p53 and found that it doesn’t play nicely with CRISPR-Cas9. P53 is responsible for scrambling emergency services when DNA is damaged, which CRISPR-Cas9 does when cutting into DNA strands and adding some new DNA. The emergency response is a take-no-prisoners approach which either ‘fixes’ the DNA, rendering the gene therapy useless, or kills the cell. Astute readers may notice this also makes the therapy useless. That could answer why gene editing can be inefficient, and that’s also where the cancer risk comes in. The only cells that survive this process have faulty p53 genes, thus compromising the cells’ ability to fight future tumors. This was only observed with the DNA insertion process, so don’t sound the death knell for CRISPR just yet.
For those interested in solving ALS (aka Lou Gehrig’s disease), last week was pretty good. While fewer than 20,000 people each year in the US are diagnosed with ALS, the impact of the disease is devastating. Researchers from Syracuse University, St. Jude’s, and SUNY Update Medical Center published a paper in Molecular Cell describing how ubiquitin eliminates droplets of Ubiquilin-2 (UBQLN2) in solution. This is important because UBQLN2 is found in motor neuron inclusions of ALS patients. The hope is that the research can lead to a better understanding of ALS’ molecular mechanisms. In a separate study, NIH-funded researchers at Stanford “used the gene editing tool CRISPR to rapidly identify genes in the human genome that might modify the severity of amyotrophic lateral sclerosis (ALS) caused by mutations in a gene called C9orf72.” Go get ’em. We couldn’t say it any better: #ALSsucks
While you may struggle to keep the extra pounds from coming on this holiday season, pigs don’t really have a choice. They apparently lack a gene called UCP1, which helps most mammals to regulate their body temperatures in cold weather. So the next best thing is typically insulation via packing the fat on, but this costs farmers a ton in feed, not to mention heating costs. Sensing an opportunity, researchers from the Chinese Academy of Sciences in Beijing used CRISPR/Cas-9 gene editing to give pigs a mouse version of the gene. The result? Healthy piglets with 24% less fat as compared to competing brands. That could mean happier pigs, that cost less, and are healthier to eat. No word yet on how CRISP-y the bacon was.
Ok, we may not exactly be at the point where we’re determining employment by genetic status, but CRISPR still gives some ethicists pause when it comes to human applications. However, a team of researchers led by Shoukhrat Mitalipov—whose greatest hits include creating “three-parent” monkeys and a technique for creating stem cells out of skin cells—decided they weren’t gonna let China have all the fun with pushing ethical boundaries. The team’s work culminated in the first gene-editing of a human embryo performed on US soil. They also did it better than their Chinese counterparts have been able to so far, with fewer unintended errors in portions of the DNA that weren’t being actively operated on.
If Neil Armstrong were a scientist, we’re pretty sure he would’ve said that about this breakthrough study. For the first time ever, the spread of the HIV virus was stopped in its tracks in a living animal, including in a humanized model. Kudos to Dr. Wenhui Hu and his team at LKSOM. This was done by using the gene editing technology CRISPR/Cas9. After replicating the findings from their previous proof-of-concept study, the team tested mice infected with EcoHIV (mouse equivalent to human HIV-1) and mice that were engrafted with human immune and T cells (i.e., “humanized”) then HIV-1. In both tests they were able to successfully excise and block further infection. Take that, HIV.
Bayer plans to unlock some of the potential within its ranks by establishing start-up-like entities. Bayer is trying the spin-out approach to developing next-gen solutions in human, animal, and agriculture technologies such as stem cells, RNA inhibition/activation, the microbiome, and DNA editing. One of the first, and probably best-funded is Casebia, a joint venture founded by Bayer and CRISPR Therapeutics. Casebia was initially funded with $300M from Bayer and another $35M was spent to give Bayer an unspecified stake in CRISPR. Casebia has access to gene-editing technology from CRISPR in specific disease areas, as well as access to protein engineering expertise and relevant disease know-how through Bayer. Prescription for success? Not sure, but take two of these and call me in the morning.