CRISPR Gene-Editing: Moving Outside Our Bodies and Into the World

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Scientists’ ability to edit our genes is increasingly accurate, efficient, and practical. With the development of the CRISPR/Cas9 gene-editing system, researchers are finding new ways to edit our DNA to fix mutations, knock out defective genes, and replace faulty sections of DNA that contribute to disease.

However, scientists are not limited to the human genome when it comes to gene editing with CRISPR. They can apply this technology to a wide variety of fields such as mosquito control, reviving extinct animals, and even modifying our food. They are expanding this technology from editing genes inside our bodies to editing genes out in the world.

The CRISPR/Cas9 system is a tool that travels along a cell’s DNA looking for a target area. Scientists can designate the stretch of DNA that CRISPR is looking for. When CRISPR finds its match, it uses a protein called Cas9 to act as “molecular scissors” to snip the DNA in the desired location. Scientists then put a healthy gene into the cell, which the cell’s own repair crew inserts into the proper place. In an interview on “CBS This Morning,” Jennifer Doudna, a key player in the creation of the CRISPR/Cas9 system, likens the process to editing a film strip. She says, “You see a particular segment of the film that you want to replace. And if you had a film splicer, you would go in and literally cut it out and piece it back together — maybe with a new clip.”

Before CRISPR, scientists were limited by inaccurate, expensive, and error-prone methods of gene-therapy. Now, using their knowledge of the human genome and the precision of CRISPR, scientists can target specific genes. In mice, researchers have already targeted genes responsible for conditions like Huntington’s disease or hemophilia and have replaced them with non-diseased versions. These molecular scissors work in plants, animals, and humans; the possibilities are endless.

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One non-human application for CRISPR is the modification of mosquitoes to reduce the spread of diseases such as malaria. According to the World Health Organization, an estimated 438,000 people died from malaria in 2015. Mosquito nets and insecticide sprays drastically reduce the number of malarial infections throughout the world, but more can be done. One strategy is to alter the mosquito so it cannot spread the disease, which Ethan Bier, a professor of cell biology at the University of California San Diego, describes as “genetic immunization.” The idea, he explains, is to genetically alter the germ line of the mosquito to make it immune to the malarial parasite. Bier and his colleagues altered mosquito embryos in the lab so they contain an anti-malarial gene. When a mosquito has a blood meal, the gene activates and produces antibodies to attack any active malarial parasites in the blood; killing them before the mosquito can transmit them to humans. If released, this strain of mosquito could introduce the anti-malarial gene into the wild population by passing the gene to its offspring.

Another option is to kill off the mosquito — Bier describes it as “genetic insecticide.” Target Malaria, a consortium funded by the Gates Foundation, aims to combat malaria using this approach. The goal: to modify the mosquito to disrupt its ability to reproduce. “We use CRISPR to cut the DNA,” says Delphine Thizy, the public engagement manager for Target Malaria. “It basically targets a gene sequence responsible for female fertility.” Any female mosquito that receives the gene edit becomes sterile. Any male that receives the edit can still reproduce but he passes the modification to his offspring, which continues to sterilize females through future generations until the mosquito population dies out.

Image Credit: Wikimedia Commons

In perhaps the most futuristic application, scientists are exploring this technology as a way to possibly bring back extinct animals. For the past several years, George Church’s lab at the Harvard Wyss Institute has explored the possibility of bringing back the wooly mammoth. He and his colleagues are altering the genome of the Asian elephant, the mammoth’s closest living relative, to give it traits the mammoth once had. In 2015 an international research team sequenced the full mammoth genome using hair they plucked from a mummified mammoth buried in the Siberian permafrost. Church’s team compared the mammoth DNA to that of Asian elephants, and characterized the differences between the species. They’re now using CRISPR to copy and paste specific mammoth traits into the cells of the elephant. These traits include adding hair, increasing fat deposits, and altering the blood cells so they can efficiently circulate in lower temperatures – basically, traits that would allow an elephant to live in a cold environment.

Bobby Dhadwar, a member of the “Mammoth Revivalists Team” at Church’s lab, says that before CRISPR, the idea of bringing back an extinct animal was laughable, but “now that we have CRISPR in our toolbox, this is something that we could actually do.” This research will take a long time to complete mainly because implanting an edited embryo into an elephant and waiting to see if the elephant calf is born with physical changes involves a two-year gestational process.

The use of CRISPR extends beyond the animal kingdom. Just last month Monsanto, the multinational agricultural and biotechnology company, received the first license to use CRISPR agriculturally. Their goals for CRISPR include creating crops with drought tolerance, disease resistance, and even improved flavor. Altering crops in the lab is not new for Monsanto: they’ve used biotechnology to create genetically modified crops for the last 20 years. In agriculture, genetically modified organisms (GMOs) are crops that scientists modify to include genes from species unrelated to the crop. This is something that could not occur in nature. Alternatively, gene editing with CRISPR is cutting, pasting, and altering the existing crop genome without the introduction of foreign genes. “We’re excited about it,” says Camille Scott, a member of the science communication team at Monsanto, “it’s really a very precise tool that should reap a lot of benefits.”

The precision and ease of editing genomes with CRISPR brings forth many ethical questions. Concerns range from claims that scientists are “playing God” to the idea that these applications are a slippery slope to designer babies or human-animal hybrids. “Any type of genetic engineering is not a black and white thing,” says Kelly Folkers, a bioethicist at New York University, “it depends why you’re doing it.” She draws a comparison between altering mosquitoes to prevent malaria and creating designer babies. “Is it being used in a way that’s going to help the greatest number of people, or is it contributing to making inequalities worse?” Folkers asks.

No one knows the full potential of this technology. It is the unknown, yet potentially vast capabilities, where our fears lie. However, one thing is clear across all platforms using CRISPR: open public engagement as well as transparency in the use of this technology is necessary for public acceptance.

2 Comments

  • This is a very interesting topic, I see the pros and cons of this technology , the idea of stoping the spread of disease is amazing. But, I’m not convinced about the application to our food source . I am intreged with the idea of bringing back extinct species. And excited to see what the future will bring!
    Thanks for the information, Emily….

  • Food is already modified, if food had not been genetically modified, your food would rot faster and would have a bad quality/taste bad. The reason to modify food even further is to improve problems that are still present with harvesters of produce which is as mentioned in the article, resist drought and avoid plagues, this would essentially long term reduce costs to prices in grocery store shelves which is a win win for everyone. People need to rethink their understanding of things, only because media says beware of GMO ‘s only to have news that generate good rating, avg consumers become misinformed and this happens.

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