Researchers from the Keck School of Medicine have found a way to genetically modify mice so the rodents’ immune systems act like human immune systems, a discovery that will impact medical testing.
Doctors Weiming Yuan, Xiangshu Wen, Seil Kim and Agnieszka Lawrenczyk published the study this month in the Proceedings of the National Academy of Sciences. The research took about two years and the project will be completed within four years.
Yuan, the project’s chief investigator, began work on the mice a few years ago, after he recognized that current clinical trials were not successful. Yuan attributed this to minor differences between human and rodent immune systems. This difference led him to attempt to humanize the mouse model.
“Making a mouse is a challenging project,” Yuan said. “This will be helping a lot of scientists to further clinical trials.”
The mice contribute to research toward finding better treatments for cancer. When tested on mice, the drug α-GalCer successfully rid the animal of cancerous cells. The same results, however, were not obtained when the medication was used on human subjects, showing differences between the two species’ immune systems.
The mice modification project required the successful insertion of a new functioning gene. This type of modification is far more challenging than so-called “knock-out” genetic modification, which is modification that works by eliminating a gene’s function. Yuan said the next step will be to further humanize the T-cell receptor, which activates lymphocytes that initiate immune system responses.
The team used the difficulty of the project as motivation to succeed. Yuan said they were all very enthusiastic about their research despite difficulty working with the small size of their grant.
“[We] definitely needed more funding — it’s the practical challenges,” Yuan said. “Lots of scientists are concerned about the funding situation.”
The team hopes to further their work in the humanization of the rodents’ immune system.
“We will branch out, but right now we have more work to further humanize the mice,” Yuan said. “We still have quite a lot of work to do before we branch out.”
The dedication and enthusiasm of the team is only gaining momentum. “The future model will be even more reliable,” Yuan said.