Genetics: Scientists wanted friendly hamsters but made them much more aggressive

CRISPR/Cas9 edits genes by precisely cutting DNA and then letting natural DNA repair processes take over. The system consists of two parts: the Cas9 enzyme and a guide RNA which is supposed to enable “transformative therapies”. It is supposed to be “a simple two-component system” used for “effective” targeted gene editing. Clearly, this definition does not apply in many cases as this outcome revealed.

The “counterintuitive results” show that the scientists “ don’t understand this system as well as we thought,” the lead researcher admitted.

By eliminating vasopressin activity the researchers had hoped it would make hamsters behave more peacefully. According to a statement from Georgia State University (GSU), a team of neuroscience researchers were however “really surprised” by the results of a gene-editing experiment that unexpectedly created hyper-aggressive hamsters.

The GSU research, published in Proceedings of the National Academy of Sciences (PNAS), aimed to better understand the biology of mammalian social behavior.

Scientists used Syrian hamsters to experiment with CRISPR/Cas9,  and eliminated a receptor for vasopressin, a hormone associated with increased aggression. Scientists believed that by doing so, they would “radically” change the social behavior of Syrian hamsters, making them more calm. Their behavior certainly changed… for the worse.

“We were really surprised by the results,” said GSU ​​professor H. Elliott Albers, the study’s lead author. “We predicted that if we eliminated vasopressin activity, we would reduce both aggression and social communication, but the opposite happened”. Hamsters lacking the receptor displayed “high levels of aggression” towards same-sex hamsters compared to their counterparts with intact receptors, the study says.

“This suggests a surprising conclusion. Although we know that vasopressin increases social behaviors by acting in a number of brain regions, it is possible that the more global effects of the Avpr1a receptor are inhibitory.”

Developing genetically modified hamsters has “not been easy,” Albers said. He added that the role of vasopressin in social behavior is essential to understand new treatment strategies for patients.

As a rule, hamsters are very territorial and intolerant of each other; attacks against each other are commonplace. Same-sex groups of siblings can stay with each other until they are about eight weeks old, at which point they will become territorial and fight with one another, sometimes to the death.

In March 2020, researchers from the University of Hong Kong maintained that Syrian hamsters could be a model organism for Covid-19 research.

The use of CRISPR/Cas9 in humans is a significant step away from treating cells in a dish, according to Fyodor Urnov, who studies genome editing at the University of California, Berkeley. “It is akin to space flight versus a regular plane trip. But last year Urnov warned that the “technical challenges, and inherent safety concerns, are much greater”.