Subscribe to our daily newsletter
CRISPR May Cause Hundreds of Unintended Mutations Into the Genome, New Study Finds
In case you haven’t already heard of CRISPR-Cas9, it is the revolutionary gene-editing technology, discovered just a few years ago, that allows scientists to edit the DNA of any species with an unprecedented precision and efficiency. Today, thousands of researchers around the world are doing experiments with CRISPR, in the hope to cure us from genetic diseases and even deliver us designer babies. The first clinical trial to employ CRISPR-Cas9 is now underway in China, hoping to fight targeted cancers with modified immune cells.
The gene-editing method is based on the protective mechanism of bacteria against viruses. An RNA molecule carries segments of DNA from a previously encountered virus together with an enzyme (Cas9). Once the molecule encounters that same sequence of DNA, the enzyme gets activated and cuts it out. Researchers discovered that they can use this system to cut any DNA sequence at a precisely chosen location.
While the tool is touted for its precision, it is far from error free. Mutations do occur around the areas where the DNA has been cut and needs to be repaired. And sometimes CRISPR may hit unintended parts of the genome. Computer algorithms identify the most likely areas for these off-target mutations, which are later examined by researchers for deletions and insertions. However, whole-genome sequencing (WGS) - examining the entire DNA of living animals that had undergone gene editing - hadn't been done.
In a recently published study in the journal Nature Methods, titled “Unexpected mutations after CRISPR–Cas9 editing in vivo” scientists used whole-genome sequencing to study the mutations that had occurred in the DNA of mice that had undergone CRISPR gene editing.
Genetic Engineering and Biotechnology News reports that “the investigators were able to determine that CRISPR had successfully corrected a gene that causes blindness, but found that the genomes of two independent gene therapy recipients had sustained more than 1500 single-nucleotide mutations and more than 100 larger deletions and insertions. None of these DNA mutations were predicted by computer algorithms that are widely used by researchers to look for off-target effects.”
Co-author of the study Vinit Mahajan, M.D., Ph.D. said:
"We're still upbeat about CRISPR, we're physicians, and we know that every new therapy has some potential side effects—but we need to be aware of what they are."
The authors are encouraging scientists to use the WGS method to determine all off-target effects of their CRISPR experiments.
In the last few days, however, some scientists have raised concerns about the validity of the study, questioning its methodology. Dr Gaetan Burgio, Group leader and head of the transgenesis facility at the Australian National University said in a Journal club review of the paper:
“The claims over this paper are unsurprising as Cas9 enzyme could remain in the cells for days and create random indels in the genome. However, the main issues for me resides in the overestimation of the number of off target effects due to the lack of rigor in the experimental design to detect these unexpected mutations. In short my main point is these unintended mutation are likely to have preexisted prior to the injection of CRISPR system.”
One thing is sure – there is a lot more work to be done to ensure the safety of the CRISPR/Cas9 technology.
Photo Credit: Pixabay
The team caught a glimpse of a process that takes 18,000,000,000,000,000,000,000 years.
- In Italy, a team of scientists is using a highly sophisticated detector to hunt for dark matter.
- The team observed an ultra-rare particle interaction that reveals the half-life of a xenon-124 atom to be 18 sextillion years.
- The half-life of a process is how long it takes for half of the radioactive nuclei present in a sample to decay.
A study looks at the ingredients of a good scare.
Catching fear in a bottle<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDYyNzg1Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyOTQwMTcyMn0.WtpJ1E_dhK2o09fBpKARynj4_p5NXeklgsXsbd7xr9w/img.jpg?width=980" id="8ff51" class="rm-shortcode" data-rm-shortcode-id="f10dd9188b173f4a36e85e9325507c6b" data-rm-shortcode-name="rebelmouse-image" />
Credit: Photo Boards/Unsplash<p>Previous studies have tracked physiological signs of fear arousal, but none have established a one-to-one correlation between that arousal and specific, actual fear events.</p><p>Andersen says that much of the research has been conducted in lab settings with weak fear stimuli, observing subjects as they experience things like scary videos. Scares in these situations tend to be weak and difficult to measure. Even harder to track in these situations is the link between enjoyment and fear. </p>
Eyes everywhere<iframe src="https://player.vimeo.com/video/109695164" width="100%" height="480" frameborder="0" scrolling="no" class="rm-shortcode" data-rm-shortcode-id="267ba87cfb8591ed5830499574d2272a"></iframe><p>Andersen and his colleagues conducted their experiments at <a href="https://dystopia.dk" target="_blank" rel="noopener noreferrer">Dystopia</a> Haunted House, a commercial attraction in Vejle, Denmark constructed in an old, run-down factory. The Recreational Fear Lab has a long-standing partnership with the spook shack.</p><p>They outfitted 100 volunteers with heart monitors and sent them on their terrifying way through the 50-room horror mansion. The facility incorporates a number of fright mechanisms including frequent jump scares in which a sudden threat takes a visitor by surprise.</p><p>Researchers surreptitiously observed their participants on closed-circuit video as they made their way through the attraction. They tracked each individual's scares, scoring them for intensity according to their visible reactions. After exiting the attraction, individuals self-reported their experiences in the haunted house.</p><p>Combining these self-reports with observer notes and each participant's heart-rate data gave the researchers subjective, behavioral, and physiological insights into the ways in which fear is experienced, and when it's a good thing or not.</p>
A pair of inverted U-shapes<p>In analyzing their data, the researchers saw two separate inverted u-shape curves. One depicted participants' enjoyment based on their self-reports and observed behavior. A similar u-curve was detected in their heart rates showing that just the right amount of heartbeat acceleration is associated with fun, but too much is too much. It's the terror Goldilocks zone.</p><p>Says Andersen, "If people are not very scared, they do not enjoy the attraction as much, and the same happens if they are too scared. Instead, it seems to be the case that a 'just-right' amount of fear is central for maximizing enjoyment."</p><p>The research suggests that being scared is enjoyable when it represents just a quick minor physiological deviation from one's normal state. When it goes on too long, however, or triggers too severe a physiological change, it becomes disturbing. Game over.</p><p>Andersen notes that this is not dissimilar to the factors known to make interpersonal play enjoyable: just the right amount of uncertainty and surprise. These are, maybe not coincidentally, also the ingredients of a successful joke.</p>
A meteorite that smashed into a frozen lake in Michigan may explain the origins of life on Earth, finds study.
- A new paper reveals a meteorite that crashed in Michigan in 2018 contained organic matter.
- The findings support the panspermia theory and could explain the origins of life on Earth.
- The organic compounds on the meteorite were well-preserved.
Meteor streaks through Michigan sky<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="80b7f30820153b35fc515592d7475f53"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/EPu2qnqMYBo?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span>
The meteorite that smashed into Strawberry Lake carried pristine extraterrestrial organic compounds.
Credit: Field Museum