Pigs are Hogging the GMO Show

When genetic engineering is mentioned, noble goals of feeding the world with more productive crops or curing terminal illnesses through gene therapy may come to mind. But some Chinese scientists recently embarked upon a less noble, although much cuter application: genetically edited pet micropigs.

The Beijing Genomics Institute (BGI) in Shenzhen announced that it plans to sell its pet micropigs for 10,000 yuan ($1,600 US). Weighing in at 15 kilograms, or about 33 pounds, the full-sized micropig would be equivalent to many medium-sized dogs.

“Micropigs” garnered great attention at the Shenzhen International Biotech Leaders Summit in China. Image credit: BGI

“The micropigs are not the first genetically modified animal to make it out there,” geneticist George Church of Harvard Medical School says.  “There are these glowing zebrafish that are beautiful, absolutely gorgeous, every color of the rainbow.” These fluorescent zebrafish are not without their critics though, considering that they could easily be flushed down a toilet or released into a local body of water. But Church added, “It’s not obvious why they would be an environmental risk, they would probably not even survive in the wild.”

Geneticists at BGI used enzymes called TALENs (transcription activator-like effector nucleases) to disrupt one of two copies of the growth receptor gene (GHR) in the pig genome (there are two copies of all genes in the genome). By using the Bama breed of pig, which is already smaller than the average swine, the researchers basically stunted the growth of the animal to create their micropig.

Church said that critics of GMOs would likely say “they are charismatic parts of the slippery slope.” And although the micropigs are attracting the most attention for their entertainment purposes as pets, they also serve a purpose for the biomedical research community as a model organism. While Mus musculus, the lab mouse, and Drosophila melanogaster, the fruit fly, might be more common examples of model organisms that scientists use to study problems related to human health and disease, a readily available animal is needed that is more similar to humans (and less controversial and expensive than primates), and that is where the pig comes in as an unlikely hero.

 

The fluorescent GloFish shine bright under a blacklight.
The fluorescent GloFish shine bright under a blacklight. Image credit: Wikipedia

It might be unfair to call the pig an unlikely hero, since the National Swine Resource and Research Center (NSRRC) in Columbia, Missouri was established by the NIH back in 2003 to promote the use of swine models in biomedical research. Pigs serve two primary purposes in biomedicine: 1) compared to many model organisms, pig physiology is more similar to human physiology, so they make good research subjects for specific diseases, and 2) due to their similar physiology and similar size of organs such as the heart and liver, pig organ transplants may be viable options for humans if the immune system rejection can be overcome.

Due to their gastrointestinal physiology and the fact that they eat just about anything (much like some of us), pigs make better models for diabetes research than most mice. In Munich, Germany a large biobank from the Ludwig Maximilian University is a sort of warehouse full of animal tissues and organs for research purposes.  Known as the Munich “MIDY-PIG” Biobank (MIDY is a genetic deficiency of insulin), the facility is leading the way to provide researchers with samples from MIDY-pigs that suffer from insulin deficient diabetes and thus require an insulin injection. Diabetes researchers can order tissues and organs from the biobank for the cost of shipping.

Other groups are looking to use pig organs for human transplants, a process known as “xenotransplantation,” where an organ from one species is translated into another. On October 5, George Church announced that his research team and company eGenesis that he co-founded were able to use CRISPR/Cas9 gene-editing system to potentially alleviate some of the immune reaction concerns of transplanting a pig organ into a human. At a seminar on synthetic biology at the Harvard Law School on October 8, Church said that “up to almost two million people are waiting for transplants.”

Banner_Pigs
Image credit: Hendrix Genetics

“So to put this into perspective, Novartis, Genzyme and other companies spent about a billion dollars on a program that looked quite good between 1995 and 2000,” Church said. “They had great progress and a plan until they slowly started to realize they had these endogenous retroviruses… And they showed that those viruses could get out of pig cells and into human cells, so it wasn’t just a hypothetical. In particular, if you transplanted an organ from a pig into a human they might be immune-compromised, at least that’s the way it looked 15 years ago.”

But thanks to CRISPR/Cas9, Church’s group was able to “to get rid of the viruses that are built into the pigs for safe transplantation.” The CRISPR/Cas9 technology, which has only been in use for about 3 years, allows geneticists to “make genetic changes in almost any organism,” he said. Specifically, they used it to disrupt 62 genes in the pig genome known as porcine endogenous retroviruses (PERVS) which may cause an immune reaction if a pig liver was transplanted into a human.

When asked why the risky genes were not removed altogether Church said, “We didn’t want to remove them because they might have some actual function, so we mutated the part that allows them to hop around and allows them to escape or move into other cells or move around within the genome, so it’s a very small change in one gene of every virus”

In another unpublished study, the team used CRISPR/Cas9 on a different set of 20 genes for pig cell surface proteins that would likely elicit an immune reaction in humans.

“CRISPR is a revolution,” Church said. “Its main application that everyone talks about is for gene therapy in humans but it has all these other applications…in this case to get rid of the viruses that are built into the pigs for safe transplantation.”

And micropig pets. Although those were technically edited via TALENs and not CRISPR/Cas9, it seems that genetic engineering is at the beginning of a new surge. The proof is in the pig.

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