Hornless dairy cattle, mosquitoes resistant to malaria, mice cured of muscular dystrophy, PRRS-resistant pigs, fast-growing salmon, livestock that require less food and have less of an environmental footprint—these are just a few examples of advantages created by the new technological tool known as gene editing. Gene editing is different than genetically-modified organisms (GMO), which are created by inserting genetic material from species A into species B to create a desired effect. Gene editing, on the other hand, typically does not involve “foreign” genes. Instead, researchers have discovered how to delete or edit individual components of DNA.
A Brief History of Gene Editing
Currently there are three main gene editing technologies: zinc finger nucleases, TALENs (transcription activator like effector nucleases) and CRISPR (clustered, regularly interspersed short palindromic repeats). Zinc finger nucleases is the oldest gene editing technology, developed around 1996. It is a protein with a DNA-cutting enzyme and a DNA-grabbing area that scientists can tailor to recognize different genes. The proteins are clunky, can be difficult to engineer, and off-target cuts are possible. TALENs was the next technology to come around, in 2010. TALENs is also a protein with a DNA-cutting enzyme and DNA-grabbing area, but is easier to engineer than zinc finger nucleases. Most recently, CRISPR was developed. CRISPR is a DNA-cutting protein guided by an RNA molecule that can locate the exact intended gene. CRISPR replaces the DNA-targeting proteins with RNA that homes in on desired genes. CRISPR is more affordable and more precise than earlier technologies. Multiple DNA changes can be made at once. This video competently explains the CRISPR DNA-editing system in 90 seconds.
This technology is a game-changer.
What sets gene editing apart from other genetic projects is that generally, in gene editing, no foreign genes from other species are introduced into the target animal. It is like a controlled mutation…something that could happen naturally. That is because this new technology is derived from a much older natural process. The original system is a bacterial technique for defense against viruses. Bacteria essentially employ CRISPR as part of their immune system. A CRISPR sequence is a string of non-coded DNA that is a palindrome (the same forwards and backwards) followed by a repetitive segment, followed by the DNA palindrome, followed by a different spacer, followed by the same palindrome, followed by a different spacer, and the pattern continues. When a virus attacks, bacteria can incorporate sequences of viral DNA into their own genetic material, sandwiching them between the repetitive segments. The next time the bacteria encounter that virus, they use the DNA in these clusters to make RNAs that recognize the matching viral sequences. The bacterial system thus fends off viruses and pieces of stray nucleic acid pieces called plasmids.
Genetic editing in animals has gone on for thousands of years—the selective breeding of livestock leads to changes in a breed’s genetic makeup similar to what can be done with modern technology. But gene editing means it takes just a few years to do what breeders would need 100 years to do. The process mimics natural genetic changes so closely it would be nearly impossible to tell whether the animal’s DNA had been altered. As a recent New York Times article pointed out, these genetically-edited animals are being cultivated to feed humans, to fight diseases, and, perhaps, to serve as pets.
Examples of Successful Gene Editing
The examples of successful editing are impressive and make me wonder at the potential application in animals and humans.
Hornless Dairy Cattle. The researchers at a start-up company called Recombinetics switched the bit of genetic code that makes dairy cattle have horns for the code that makes Angus beef cattle hornless. This will allow the dairy cattle to avoid the process of being dehorned. Recombinetics is reportedly working on pigs that will never have to be castrated and livestock resistant to hoof and mouth disease.
Pigs and PRRS. Researchers and scientists from the University of Missouri, Kansas State University, and Genus pIc recently bred genetically-edited pigs that are not affected by the disease called porcine reproductive and respiratory syndrome (PRRS). A protein called CD163 allows PRRS to spread. Scientists edited the gene that makes CD163 to prevent pigs from being susceptible to the virus. The piglets born without the protein were exposed to PRRS and remained healthy. Gene editing stopped the virus from spreading, and the pigs without the protein saw no developmental changes. PRRS costs North American pork producers more than $660 million each year, and there is no effective vaccine to prevent the virus. According to Genus, this genetic innovation will lower the impact on the animals, improve their well-being, and improve farm productivity, which will help meet global demand for pork products. The Genus announcement from December 2015 is available here.
AquAdvantage Salmon. In November 2015, federal regulators approved a genetically edited salmon as fit for human consumption, making it the first genetically altered animal to be cleared for the dinner table. The “AquAdvantage salmon” is an Atlantic salmon that has been genetically engineered so it grows to market size in as little as half the time of a non-edited fish. The AquAdvantage salmon contains growth hormone DNA from the Chinook salmon and a genetic switch from the ocean pout, an eel-like creature, that keeps the transplanted gene continuously active, whereas the salmon’s own growth hormone gene is active only parts of the year. Government officials announced the fish would not have to be labeled as being genetically engineered, a policy consistent with its stance on foods made from genetically engineered crops.
Malaria Resistant Mosquito. Researchers in California announced they genetically edited a mosquito so that it could not carry the parasite that causes malaria. The mosquito was engineered to carry two DNA modifications. One is a set of genes that send out antibodies to the malarial parasite. Mosquitoes with these genes are resistant to the parasite and so cannot spread malaria. The other modification is a “gene drive” that should propel the malaria-resistance genes through a natural mosquito population.
M.D. Cured Mice. CRISPR can also be used to treat genetic disease inside a fully-developed animal. Scientists at Duke have used CRISPR to treat mice with Duchenne muscular dystrophy, delivering the gene-editing system directed to affected tissue with a non-harmful virus. The CRISPR system was programmed to cut out the small section of dysfunctional DNA, which prompts the body's natural repair system to stitch the remaining gene back together, creating a shortened but functional version of the gene.
These examples demonstrate one obvious benefit of gene editing is improved animal health. Slight genetic edits can make livestock resistant to diseases. Resistance to disease reduces the need for antibiotics, which would minimize any development of antibiotic resistance and antibiotic residue in food products. Another benefit of CRISPR and other genetic editing technology is an increase in economic returns for farmers, growers, and integrators by improving livestock health, reducing the need for antibiotics, and increasing animal size while minimizing inputs. Genetic editing can make farming more efficient to help feed a growing world population with less of a toll on the environment. The technology could benefit human health as well (sickle-cell anemia, cystic fibrosis, and HIV are three diseases often discussed by scientists as being appropriate tests for gene editing in humans).
The many recent announcements of successful animal DNA-edits lead to the obvious question: what next? How can gene editing be applied in other animals? Could gene editing be one answer to the projected increased demand for animal protein in the upcoming next years? What are the risks of gene editing and how should these be addressed? Should the government get involved? Will this technology be used to improve human lives too? When? I’d love to hear your thoughts on this topic. My next post about animal gene editing (coming next week) will focus on the regulation of genetically edited animals and reactions from proponents and opponents.