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Tool for controlling genetic inheritance tested in mice for the first time

"With further development we think it will be possible to make animal models of complex human genetic diseases, like arthritis and cancer, that are not currently possible," said researcher Kimberly Cooper.

By Brooks Hays
Tool for controlling genetic inheritance tested in mice for the first time
Scientists used gene drive technology to increase the odds of mice offspring inheriting the gene sequence that causes black fur. Photo by Anna Tyurina/Shutterstock

Jan. 24 (UPI) -- Scientists at the University of California, San Diego, have for the first time tested gene drive, a genomic editing method used to control inheritance, in mice. Their efforts, detailed this week in the journal Nature, proved a partial success.

Gene drive relies on the insertion of a self-replicating DNA sequence, called "CopyCat" DNA, using CRISPR/Cas9 gene-editing technology. By copying and pasting the same genetic coding from one chromosome to the other, the technology can -- in theory -- boost the probability of a target gene or genes being passed onto the parent's offspring.

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If mom inherited a single copy of a target gene from her parents, her offspring have only a 50 percent chance of inheriting the gene sequence and accompanying genetic traits. But if both mom chromosomes carry the target gene, the odds of her offspring receiving at least one copy of the target gene sequence jump to 100 percent.

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Scientists have previously used gene drive to surpass the reproductive success of female mosquitos, reducing population numbers. But designing and inserting CopyCat DNA for the use of gene drive in mammals is more complicated.

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"Our motivation was to develop this as a tool for laboratory researchers to control the inheritance of multiple genes in mice," Kimberly Cooper, an assistant professor at UCSD, said in a news release. "With further development we think it will be possible to make animal models of complex human genetic diseases, like arthritis and cancer, that are not currently possible."

For the latest gene drive tests on mice, scientists designed a CopyCat element that damaged the Tyrosinase gene in one chromosome. The Tyrosinase gene controls fur color in mice. The genetic damage triggered a second CopyCat element, an engineered repair mechanism, causing the genome to copy the Tyrosinase DNA from the undamaged chromosome to the compromised chromosome.

Though the technique wasn't foolproof, when the genetically modified females were allowed to breed, 86 percent of their offspring inherited the CopyCat element.

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Scientists had a harder time increasing the odds of inheritance by manipulating the chromosomes transported by the sperm from male mice.

While the press release issued by UCSD hailed the experiments as a success, several news reports suggested the tests proved gene drive technology still has a long way to go for the purpose of population control in mammals.

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First, for safety purposes, scientists didn't actually test the same gene drive technology used in insects. The tested to two components of gene drive technology separately. By separating the components that cut and copy the DNA, researchers ensured the genetic traits would not spread uncontrollably.

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Researchers also only targeted a small genetic sequence. Many important traits are controlled by a multitude of genes and it's unclear how well gene drive technology, as it currently exists, could work to influence traits more complicated than fur color.

And because the gene drive's efficiency is still relatively low, it's likely mammals would build resistance before a trait was able to spread throughout an entire population -- a process that would require the CopyCat DNA to be passed down across several successive generations.

The scientists responsible for the latest research admitted their technology still needs a lot of tweaking before it has any practical value.

"If someone were to try to build a gene drive using this type of mechanism right now, it wouldn't spread through a population very quickly and probably wouldn't persist," Cooper told Quanta Magazine.

But even if gene drive technology can't yet be used for population control or to achieve 100 percent inheritance rates, scientists think the method in its current form could still inspire a variety of new genetic experiments and even helps scientists better understand the genetic organs of disease.

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