May 302017
 

via Drug Target Review

As CRISPR-Cas9 starts to move into clinical trials, a new study published in Nature Methods has found that the gene-editing technology can introduce hundreds of unintended mutations into the genome.

“We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome,” says co-author Stephen Tsang, MD, PhD, the Laszlo T. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology at Columbia University Medical Center and in Columbia’s Institute of Genomic Medicine and the Institute of Human Nutrition.

CRISPR-Cas9 editing technology — by virtue of its speed and unprecedented precision — has been a boon for scientists trying to understand the role of genes in disease. The technique has also raised hope for more powerful gene therapies that can delete or repair flawed genes, not just add new genes.

The first clinical trial to deploy CRISPR is now underway in China, and a U.S. trial is slated to start next year. But even though CRISPR can precisely target specific stretches of DNA, it sometimes hits other parts of the genome. Most studies that search for these off-target mutations use computer algorithms to identify areas most likely to be affected and then examine those areas for deletions and insertions.

“These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals,” says co-author Alexander Bassuk, MD, PhD, professor of pediatrics at the University of Iowa.

In the new study, the researchers sequenced the entire genome of mice that had undergone CRISPR gene editing in the team’s previous study and looked for all mutations, including those that only altered a single nucleotide.

The researchers determined that CRISPR had successfully corrected a gene that causes blindness, but Kellie Schaefer, a PhD student in the lab of Vinit Mahajan, MD, PhD, associate professor of ophthalmology at Stanford University, and co-author of the study, found that the genomes of two independent gene therapy recipients had sustained more than 1,500 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.

“Researchers who aren’t using whole genome sequencing to find off-target effects may be missing potentially important mutations,” Dr. Tsang says. “Even a single nucleotide change can have a huge impact.”

Dr. Bassuk says the researchers didn’t notice anything obviously wrong with their animals. “We’re still upbeat about CRISPR,” says Dr. Mahajan. “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.”

Researchers are currently working to improve the components of the CRISPR system–its gene-cutting enzyme and the RNA that guides the enzyme to the right gene–to increase the efficiency of editing.

“We hope our findings will encourage others to use whole-genome sequencing as a method to determine all the off-target effects of their CRISPR techniques and study different versions for the safest, most accurate editing,” Dr. Tsang says.

Learn more: CRISPR gene editing can cause hundreds of unintended mutations

 

The Latest on: CRISPR-Cas9
  • 2018 Robalo R222
    on January 19, 2018 at 8:00 am

    A 15-gallon insulated livewell is conveniently located under the leaning post and features LED lighting, a blue gel coat finish for bait preservation and a directional aerator head unit with a flow valve. The starboard swim platform features a telescopic ... […]

  • Floating for Winter Steelhead in the Pacific Northwest
    on January 17, 2018 at 12:47 am

    The fish must have held onto that bead for a while, which I attribute to Pro-Cure’s Anise Bloody Tuna Super Gel. I don’t know how much time ... Finally, Jake pulled out a rod rigged up for float fishing bait, with a very small piece of hollowcore ... […]

  • The health risks of cockroaches and how to eradicate them
    on January 9, 2018 at 2:45 am

    If the cockroaches are persistently still in your home despite your best cleaning efforts, you can use chemical treatments such as gel baits, which you place near where the cockroaches have their harbourage area, but away from your cutlery and food. […]

  • Univar Product of the Month: Alpine Cockroach Gel Bait Rotation 1 & 2 Reservoirs
    on January 2, 2018 at 12:00 am

    Reduced Risk cockroach gel bait* Attractive. Both bait matrices appeal to gel-bait averse and non gel-bait averse cockroaches. Fast Acting. These BASF products begin killing cockroaches within minutes after exposure to the bait. Reliable. This rotation ... […]

  • Ants killed using seaweed-based gel balls in California study
    on May 22, 2017 at 8:33 am

    Scientists have developed an eco-friendly bait that could reduce ant populations by nearly 80%. Researchers from the University of California, Riverside (UC Riverside) hope their seaweed-based hydrogel baits could replace ecologically damaging pesticides. […]

via Google News and Bing News

Other Interesting Posts

Leave a Reply

%d bloggers like this: