by Emily Mullin
November 01, 2018
from Medium Website








From turning pigs into organ donors

to changing the color of flowers,

the future of gene-editing tech

is wacky and wonderful...

There are few modern-day scientific innovations with implications as profound as the gene-editing technology CRISPR, which allows scientists to precisely cut and alter the DNA of any cell.

Scientists' use of CRISPR has taken off, in part because it's so much easier to use than earlier iterations of gene editing. Though CRISPR hasn't cured disease or ended world hunger yet, it's already being used in some amazing ways.

We've rounded up seven of the most wild examples.

1. Turning pigs into organ donors

For decades, scientists have considered the controversial idea that animals could provide a ready supply of organs to help ease the organ transplant shortage.

More than 114,000 people are currently waiting to receive a transplant in the U.S., alone. Past attempts to implant animal organs into people have failed because the human body's immune system rejects foreign tissue. (The first heart transplant ever performed in a human was in 1964, with a chimpanzee heart. The patient died within two hours.)

Another barrier is the possibility that infections from animal donors could be transmitted to human recipients.

Researchers think CRISPR could solve both of these challenges.

One company, eGenesis, spun out of Harvard geneticist George Church's lab, is using CRISPR to make pigs suitable organ donors for humans. Many pig organs, like the heart and lungs, are similar in size to human ones.

Researchers at eGenesis have used CRISPR to snip out a family of viruses found in pig DNA that could be passed to people during transplantation.

These viruses, known as porcine endogenous retroviruses, or PERVs, could jump from pigs to human cells and randomly integrate into the human genome.

The company has produced dozens of virus-free pigs so far. The company is also using CRISPR to modify genes involved in the immune system and prevent the human body from rejecting the organs.

A clinical trial of human transplants with organs produced in gene-edited pigs is, most likely, still years away.

"I think people wanted this to happen because they realized it was the ultimate medicine."

2. Making new and improved fruit

You're probably not familiar with groundcherry (physalis), but Joyce Van Eck hopes the fruit will someday become a household name.

About the size of a cherry tomato, the groundcherry is sweet with notes of pineapple and mango. It can grow in the U.S., but it's currently uncommon because the plants sprawl wildly and are hard to control.

Eck, an associate professor at Cornell University, and her collaborator Zachary Lippman at the Cold Spring Harbor Laboratory, are using CRISPR to make the groundcherry more appealing to farmers.

"We saw it as a novelty fruit that, with some improvement, could become a more specialty food crop in the U.S. and grow more widely," Eck says.

Eck and Lippman first targeted the groundcherry's self-pruning gene to make the plant more compact as it grows.

Eck says the change essentially fast-tracked the plant's domestication and made the fruit develop earlier. Next, they used CRISPR to tweak the groundcherry's genetics to make the fruit 25 percent bigger.

They published their findings (Rapid Improvement of Domestication Traits in an Orphan Crop by Genome Editing) in October 2018, in the journal Nature Plants.

Eck thinks CRISPR will be an important tool in domesticating new crops, increasing the nutritional value of food, and helping to protect crops from extreme weather and climate change.

"We rely on just a handful of staple food crops, not just within the U.S. but in other countries," she says. "I think it's really important to find other crops in case of crop failure, but also as a way to diversify diets."

CRISPR is also being studied as a way to breed cacao trees to be resistant to diseases that are increasingly affecting chocolate production.

And DuPont Pioneer, an agriculture company, has licensed CRISPR technology to breed a new and improved variety of waxy corn, which is used to thicken food products.

3. Changing flowers from violet to white

Japanese scientists are using CRISPR to change the flower color of a traditional garden plant.

Researchers programmed CRISPR to target a specific gene, known as DFR-B gene, in the Japanese morning glory. In the lab, they inserted the CRISPR system into plant embryos.

The gene-editing tool successfully disrupted the DFR-B gene, which is responsible for the color of the plant's stems, leaves, and flowers. By doing so, it changed the plant's characteristic violet color to white.

The researchers say their work (CRISPR/Cas9-mediated mutagenesis of the dihydroflavonol-4-reductase-B locus in the Japanese morning glory Ipomoea -Pharbitis- nil), published last year, reveals the huge potential of CRISPR to the study and manipulation of genes in gardening plants.

4. Modifying human embryos for healthier babies

Last year, a scientist in Oregon made headlines when he reported that his team used CRISPR to snip out a heart disease-causing genetic error in dozens of human embryos.

It was the first time CRISPR had been used in the U.S. to modify human embryos.

Shoukhrat Mitalipov, who directs the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University, zeroed in on a mutation in a gene called MYBPC3 which is responsible for an inherited heart condition called hypertrophic cardiomyopathy.

The condition occurs in about 1 in 500 people and can cause heart failure and sudden death.

"Every generation on would carry this repair because we've removed the disease-causing gene variant from that family's lineage," Mitalipov said in a university statement.

Editing cells in embryos is known as germline editing, and is controversial because the genetic changes that result can be passed on to subsequent generations.

That's different than somatic genome editing, which only affects the treated individual.

Japan may soon move forward with similar research. The country has issued draft guidelines allowing human embryos to be modified with CRISPR and other genome-editing technologies.

If adopted,

"the guidelines would restrict the manipulation of human embryos for reproduction, although this would not be legally binding," according to an October 2018 report in the journal Nature.

But science is far from using CRISPR to make designer babies  -  at least in the U.S.

That's because a congressional rider forbids the U.S. Food and Drug Administration (FDA) from even considering any human trials that would involve modifying human embryos.

5. Halting muscular dystrophy in dogs

In dogs with muscular dystrophy, a CRISPR gene-editing treatment appeared to fix the genetic mutation responsible for disease.

The findings (Gene Editing restores Dystrophin Expression in a canine model of Duchenne Muscular Dystrophy), reported in August 2018, represent a major step forward in developing a treatment for Duchenne muscular dystrophy, a devastating and life-shortening illness most common among young boys.

It's a genetic disease occurring in about 1 in 3,500 boys born, worldwide.

Duchenne is caused by a mutation in the DMD gene, which makes dystrophin, an essential protein found in muscle cells. The mutation means the gene can't make functioning dystrophin, and without it, muscles are weak and don't work properly.

Muscle loss in Duchenne is typically fatal, and men with the disorder usually only reach their early thirties.

In an effort to stop the disease in its tracks, researchers at the University of Texas Southwestern injected CRISPR into one-month-old beagles. Gene editing was able to restore dystrophin in muscle and heart tissue in the dogs by up to 92 percent.

Scientists have estimated that a 15 percent threshold would be needed to significantly help humans.

"It is really impressive how well this works," says Elizabeth McNally, director of the Center for Genetic Medicine at Northwestern University, who studies the genetics of muscular dystrophy.

Elizabeth McNally wasn't involved in the research, but serves on the board of Exonics, the company that funded the study.

"You see this change where a small amount of DNA being corrected can result in a big protein change."

McNally says she wouldn't be surprised if the approach moved to human trials in just a few years.

"I think in many ways, Duchenne is really the poster child for doing this," she says of gene editing.

6. Creating new treatments for cancer and blood disorders

Injecting CRISPR directly into the body is risky, so for now, investigators are using CRISPR to edit human cells outside the body and then infusing them back into patients.

The approach is being used in early clinical trials in the U.S., Europe, and China.

In the U.S., a trial sponsored by the University of Pennsylvania and a company called Tmunity is recruiting up to 18 people with multiple myeloma, sarcoma, and melanoma who haven't responded to traditional drugs, or have seen their cancer come back.

Investigators will extract human immune cells from the men and women and use CRISPR to genetically alter them to attack cancer cells. The edited cells will then be infused back into the patients.

Another company, CRISPR Therapeutics, is planning to use CRISPR to treat people with beta thalassemia and sickle cell disease, two related blood disorders that are caused by mutations in the same gene.

These mutations affect a person's ability to make hemoglobin, a vital protein in red blood cells that carries oxygen throughout the body. In a statement provided to Medium, the company said it started enrolling people with beta thalassemia into a clinical trial in Germany.

Meanwhile, in the U.S., CRISPR Therapeutics and Vertex Pharmaceuticals are planning to launch a trial for sickle cell by the end of 2018.

Both trials will extract bone marrow stem cells from people in the trial, edit the cells with CRISPR in the lab, and transfer them back into the patients. They hope that the process helps patients produce a type of hemoglobin.

Researchers in China began their first round of similar experiments in people last year, but have yet to report any data from the 11 ongoing trials registered on clinicaltrials.gov.

Eric Kmiec, director of the Gene Editing Institute at Christiana Care Health System in Delaware, says he's not surprised that CRISPR has moved this quickly for very serious diseases.

"I think people wanted this to happen because they realized it was the ultimate medicine," he says. "Considering the desperation and lack of other treatments for some diseases, it's encouraging."

7. Eliminating mosquitoes

Mosquito-borne diseases, especially malaria, are a deadly scourge.

Globally, malaria kills more than 400,000 people every year. To cut down on the spread, some scientists propose using a controversial technology called a gene drive.

A gene drive is a genetic engineering tool designed to spread certain genes throughout a species. Though it's not a new idea, gene drives are closer to reality now thanks to CRISPR.

In a paper (A CRISPR–Cas9 Gene Drive targeting Doublesex causes complete Population Suppression in caged Anopheles gambiae Mosquitoes) published in September 2018, researchers at Imperial College London showed that a gene drive made with CRISPR could suppress a population of Anopheles gambiae  -  the type of mosquito that transmits malaria in Sub-Saharan Africa.

Investigators used CRISPR to target alter a so-called doublesex gene, which is responsible for female development.

When female mosquitoes inherited two copies of this modified gene, they couldn't bite or lay eggs. Researchers tested the self-destructive mosquitoes in cages and found that, after eight generations, no normal females we left to reproduce and the population died out.

Genes drives haven't been released outside of laboratories yet.

There's the possibility that genetic alterations designed to crash populations could mutate and pass on an advantageous trait. But this study showed that the gene drive transmitted the genetic modification nearly 100 percent of the time, avoiding resistance.

Leaders of the African Union earlier this year endorsed gene drive research in an effort to fight malaria in their countries, but it could still be years before the technology is tested in the wild.