CRISPR: Five weird projects pushing the boundaries of gene editing

Over the past few years, targeted gene editing has gone from complicated and error-prone niche applications to easy and efficient mainstream technology. All this thanks to CRISPR, a new and easy-to-use gene-editing tool that is spreading in the scientific community like wildfire.

To date, CRISPR has mainly been used in the medical field, from uncovering causes of disease to developing new therapies. However, researchers can be a quirky and peculiar bunch, and some have spotted alternative applications for this technique. Let’s just say some uses can be a little off the wall…

CRISPR: Hercules, the super-dog

With double the amount of muscle, Hercules is the world’s first genetically engineered super-dog. Together with his sister Tiangou, the duo were created by Chinese scientists by switching off a gene called myostatin. This gene regulates the amount of muscle fibres produced and, without this break, the body just doesn’t know when to stop.

According to Xiang Gao, one of the scientists involved in the study, this gene was selected simply because it would be easy to see the result. “We believe the protocol we developed solves the major problems for dog genome modification (including transgenic). It is as efficient as CRISPR/Cas9 in other laboratory animals, such as mice and rats,” he explains.

These scientists are planning to use CRISPR to take advantage of the dog’s proximity to humans to study human diseases, but it’s easy to see how biotech companies may have different ideas. Now that the door to designer pets is firmly open, it probably won’t be long until we can “customise” our pet in terms of size, colour, as well as strength or intelligence.

There’s even a precedent for this situation, as a different research institute in China is already offering miniature pigs no bigger than a beagle. These micropigs, also created by gene-editing techniques, are selling like hot cakes with a $1,600 price tag.

CRISPR: Fluorescent beetles

Fluorescence is known to occur in many living organisms, but normally flour beetles are not among them. Until now.

A team of French researchers created a glowing beetle by adding a green fluorescent protein to its genome. Just like with Hercules, this was the first time CRISPR was applied to beetles, and the researchers just looked for something easy to spot.

Now that it’s working, the team sees immense potential in exploring this technique to study how specific types of cells change during development. “A way of doing that is to introduce a fluorescent protein that allows you to observe specific cells. If you want to label muscle cells, for example, you can use CRISPR to insert a fluorescent protein into a muscle-expressed gene and observe what happens. CRISPR provides a faster and cleaner approach to do this,” biologist Michalis Averof of the Institute of Functional Genomics in Lyon tells me. Fans of weird and uncommon species used in the lab, the same team also works with small crustaceans and is aiming to create a fluorescent version to study leg regeneration after injuries and amputations.

In Australia, embryo chicks have also been ‘CRISPRed’ with a fluorescent tag, but in this case, it was actually done with a specific application in mind. Typically, in the egg industry, male embryos have no value and

are usually culled immediately after hatching. To avoid this procedure, researchers from the Commonwealth Scientific and Industrial Research Organisation introduced a fluorescent protein in males, allowing for embryos to be sexed before hatching. In theory, male embryos can then be removed and potentially used for alternative purposes, such as vaccine production.

CRISPR: Turning males into females

Females that turn to males and males that turn to females – it’s all in a day’s work in a lab in Blacksburg, Virginia. They first had to identify the gene responsible for gender determination, but afterwards it was actually easy to use CRISPR and other genetic tools to play around with the gender in mosquito populations. “We identified a gene which we called Nix,” explains Zach Adelman. “When we knocked it out all mosquitoes became female mosquitos, and when we added it in, the mosquitos became male mosquitoes.”

It may sound amusing, but this work actually has a very serious motivation. In mosquitoes, it’s only the female that can bite and transmit diseases, so they’re trying to build large populations of non-biting sterile males to release into the wild. Malaria, Dengue and now Zika are just some of the many diseases transmitted by mosquitoes, and many groups are hard at work to develop ways to control the spread of these small and dangerous insects.

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CRISPR: Bring back the mammoth

If you’ve ever seen any of the Ice Age films, it’s impossible not to fall in love with Manny, the mammoth. About 3-4 million years ago, these magnificent animals roamed across the northern continents, foraging for grass and shrubs. With a fluffy fur coat, a thick layer of fat and incredibly small ears, they were designed for the cold.

Researchers estimate they disappeared about 10,000 years ago, but that may be about to change. A team from Harvard Medical School has attracted much attention for its grandiose idea of using CRISPR to transform Indian elephants into woolly mammoths. Correction: the goal is not to create a mammoth (which is actually impossible to do), but to develop a cold-resistant elephant. The idea is to find the genes for specific mammoth characteristics – like subcutaneous fat and thick hair – and transfer them to the Asian elephant.

Idea-man George Church claims that a battalion of cold-loving elephants able to survive Siberian winters would prevent further loss of the permafrost. It may seem counterintuitive, but as these massive beasts trample the ice looking for food, they break the snow’s insulation and allow the Arctic chill to reach deep into the earth, keeping it frozen. This explanation may seem a little far-fetched, but one thing’s for sure: if this ever becomes a reality, the journey on board the Trans-Siberian Railway would be like entering a time machine back to the Pleistocene!

Incredibly, this is not the only project trying to bring back extinct species using CRISPR. In fact, the field has its own name: de-extinction. Another example involves the passenger pigeon, a once-common bird that became extinct in the late 19th century thanks to excessive hunting. Researchers at Revive and Restore, an organisation supporting various de-extinction projects, plan to tweak the genome of modern pigeons to make them more similar to the extinct passenger pigeon.

CRISPR: Need a transplant? Head for the pig farm

Need a heart? Or a liver? Maybe a kidney? For years, doctors have dreamed of ways to reduce the long waiting list patients face to get a transplant. Growing organs in pigs was nothing more than a crazy idea until CRISPR brought it a little closer to reality.

Again from Church’s lab come extraordinary results that could change the future of medicine: they’ve managed to modify over 60 genes at once – more than ten times what had been previously achieved – to remove all pig retrovirus, which could trigger a rejection after a transplant, potentially making pigs’ organs suitable for transplantation into humans. Researchers at eGenesis, a biotech company founded by Church, are currently developing methods to make these organs as cheaply as possible.

CRISPR: What’s next?

Humans as strong as an ox or dogs as intelligent as humans? Maybe a plan to bring back the dodo? Even introducing genes to stop the spread of weeds? Who knows what could come out of the minds of researchers ‘savouring’ what CRISPR can offer and stretching the technique to the limit. Some of these and other examples may seem somewhat dubious science at first glance, but they all have a clear and specific reason behind them, including testing the technique, developing important new therapeutic approaches or even designing better conservation approaches.

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Images: Katja Schulz, Rob Pongsajapan and Connie Ma used under Creative Commons