Gene-editing of salmon being studied in Norway

Researchers at the Norwegian Institute of Marine Research in Bergen, Norway, have used the CRISPR/Cas9 method of gene editing to produce salmon that cannot produce gametes (eggs and sperm), so cannot reproduce.

If produced for commercial purposes, any escaped fish would be unable to breed with the wild salmon population. They would also not experience the issue of early sexual maturation, which can lead to poor meat quality and greater susceptibility to disease, according to Lene Kleppe, a researcher working on the project.

Currently, these fish are kept in strict bio-controlled conditions on land at the research center because they are defined as genetically modified, and strictly regulated by Norway’s Genetic Engineering Act. Interaction between wild and farmed fish is a major environmental concern in Norway, making sterile fish an attractive proposition for biocontainment, Kleppe told SeafoodSource. The only commercially used methodology for producing sterile fish is triploidization, which in Atlantic salmon, is generally induced in a laboratory through use of thermal or pressure shocks to newly fertilized eggs. However, triploid fish are often less robust.

“Our research has been ongoing since 2013, but the latest developments may offer a lot of promise for the future of salmon farming,” Kleppe said. “We are also studying other areas such as disease resistance, robustness, and omega-3 fatty acid metabolism. We want to understand if there might be potential benefits from using gene editing to support or improve any of these factors.”

Since 1953, when the molecular structure of DNA was first reported, scientists have tried to develop tools to manipulate the genetic material of cells and organisms. The discovery of the mechanism by which CRISPR/Cas9 genetic scissors work has only been around for 10 years, but the technology has allowed scientists to change the DNA of animals, plants, and microorganisms with high precision.

Such is the importance of this new method of genome editing that its discoverers, Emmanuelle Charpentier and Jennifer Doudna, were awarded the Nobel Prize in Chemistry in 2020.

One problem with producing sterile fish one egg at a time is that it is time-consuming and impractical to do on the industrial scale needed to support a growing aquaculture industry. As a result, the Norwegian scientists are also looking at the possibility of producing inherited sterility in Atlantic salmon by “rescuing” germ cells in embryos that have been edited using CRISPR/Cas9.

They found that their method opens up the possibility of large-scale production of germ-cell-free Atlantic salmon offspring, using genetically sterile broodstock that can pass the sterility trait on the next generation.

“The work is at an early stage, but we have already noticed interest from the industry. However, breeding salmon is a slow process, so we have to be patient,” Kleppe said.

While gene editing is different from genetic modification or genetic engineering because it does not result in the introduction of DNA from other species, Kleppe said public perception of gene-edited salmon may be just as big a hurdle to overcome as producing the fish. Currently, gene-edited animals are regulated in the same way as genetically modified organisms in the majority of countries around the globe.

“In Japan, gene-edited fish is already on the marketv, but most nations are still wary of it. When and if new countries start to produce and sell gene-edited products, and by doing so, gain some advantages, this may put pressure on others to follow suit,” Kleppe said. “If selling a gene-edited product, I think it is important to be transparent and to educate consumers about the way it was produced, and maybe also why it was produced in that way. This would give consumers the knowledge they need to make the decision of whether to buy it or not.”

Kleppe said she believes many people are still fearful of “GMO” food, but this she said the term relates to modifications done with old technology, whereas that used today is very precise.

“While we don’t know to what extent gene-editing will be used in in salmon farming in the future, CRISPR is an important research tool for studying the function of genes, and it can also help us to identify genes we could target in other ways,” she said.

In the United States, where AquaBounty’s AquAdvantage genetically engineered (GE) transgenic Atlantic salmon took decades to obtain FDA approval, the public still remains wary of eating it, despite reassurance from the authorities.

AquaBounty’s AquAdvantage salmon were designed to grow to market size in half the time as conventional Atlantic salmon, through the instruction of a growth hormone gene from Pacific chinook salmon and a promoter sequence, which is a fragment of DNA, from the ocean pout. Together, the gene and promoter sequence enable the salmon to grow year-round. They also have three sets of chromosomes, compared to the two sets in conventionally farmed salmon, which render then sterile.

In April 2022, the FDA issued a public statement confirming the safety of the product for human consumption.

:The salmon are safe to eat, the introduced DNA is safe for the fish itself, and the salmon meet the sponsor’s claim about faster growth,” the FDA said.

The FDA confirmed that the nutritional profile of AquAdvantage salmon is comparable to that of non-GE farm-raised Atlantic salmon, and that no significant environmental impact would arise from producing the fish in closed containment.

Photo courtesy of Erlend Astad Lorentzen/Institute of Marine Research