The study and the engineered mice can help efforts to develop new drugs against COVID-19. Credit: NYU LANGONE STAFF
Key points:
- Researchers genetically engineered the first mice that get a human-like form of COVID-19.
- Scientists swapped out the mouse ACE2 gene with the human ACE2 gene that codes for the protein that the COVID virus uses to attach to human cells.
- The humanized mouse model can be crossbred with existing mouse lines to study how the body reacts differently to COVID when patients have underlying conditions such as diabetes or obesity.
In a study, recently published in Nature, researchers have genetically engineered the first mice that get a human-like form of COVID-19.
Researchers created mice with human genetic material for the ACE2 protein, which COVID-19 viruses use to attach to cells. Unlike previous mouse models that died upon infection, the mice with this genetic alteration developed symptoms resembling those observed in young humans infected with the virus.
“That these mice survive creates the first animal model that mimic the form of COVID-19 seen in most people—down to the immune system cells activated and comparable symptoms,” said senior author Jef Boeke of NYU Langone Health. “This has been a major missing piece in efforts to develop new drugs against this virus.”
Boeke and his team utilized a new method to create a humanized mouse model of COVID-19 pathology by “overwriting” 72 kilobases of mouse ACE2 code with 180 kilobases of the human ACE2 gene and its regulatory DNA.
They employed a “genome writing” approach where they used yeast cells to assemble large DNA sequences. They cut into a spot in the DNA code around the natural mouse gene and swapped in a synthetic counterpart in steps while carefully ensuring that only cells with the synthetic gene survived. Next, they delivered the “naked” DNA into mouse embryonic stem cells using the mSwAP-In delivery method to create a mouse whose cells included an unchanged version of the human gene.
Looking ahead, the team is eager to explore how their genetically engineered mouse line can contribute to diverse future research.
“Given that mice have been the lead genetic model for decades, there are thousands of existing mouse lines that can now be crossbred with our humanized ACE2 mice to study how the body reacts differently to the virus in patients with diabetes or obesity, or as people age,” explained Boeke.