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World’s First Mammal CRISPR / Cas-9 Genetic Inheritance Control Achieved



CRISPR / Cas9 is a form of genetic editing that holds a lot of promise, such as the killing of cancer cells, but also comes with some severe warnings, such as that may cause DNA damage. So far, scientists have been using CRISPR / Cas9 in a variety of plants and animals to edit genetic information, including attempts to practice what is called 'active genetics'.

This last approach is an attempt to edit the genome that controls which of the two copies of it has passed to the next generation. But the technique is complicated and rife with obstacles so thus been used only on insects. Not anymore!

A team of biologists has now achieved the world's first CRISPR / Cas9-based approach to control genetic inheritance in a mammal.

"Our motivation was to develop this as a tool for laboratory researchers to control the inheritance. of multiple genes in mice, "said project lead assistant professor at University of California San Diego Kimberly Cooper. "With further development we think it will be possible to make animal models of complex human genetic diseases, like arthritis and cancer, which are not currently possible." To achieve their lofty goals, the researchers engineered and active genetic "CopyCat" DNA in the genes responsible for fur color in mice and successfully succeeded in controlling mice for color, making it white instead of black. Then, over a two-year period, they expanded their work to determine that the CopyCat element could be copied from one chromosome to the other in order to repair a break in the DNA targeted by CRISPR / Cas9.

As a result , they found that as much as 86 percent of the mice offspring inherited the CopyCat element from the female parent. This was a great improvement on the usual 50 percent naturally achieved.

According to UC San Diego Professor Ethan Bier, a study coauthor, the results, "the way for various applications in synthetic biology including the modular assembly of complex genetic systems for studying various biological processes. "Cooper and her team are trying to build on this first mammalian active genetic success further by extending it to multiple genes instead of the single gene alteration possible now.

"We have shown that we can convert one genotype from heterozygous to homozygous. Now we want to see if we can efficiently control the inheritance of three genes in an animal. If this can be implemented for multiple genes at once, it could revolutionize mouse genetics, "said Cooper.

Exploring evolution

The work could lead to a significant decrease in the time and cost needed for advance biomedical research on human diseases. But for Cooper and her team, it goes beyond that. Her research is also a way of exploring evolution itself.

"We are also interested in understanding the mechanisms of evolution," said Cooper. "For certain traits that have evolved over tens of millions of years, the number of genetic changes is greater than we can currently assemble in mice to understand what causes us to grow into a wing, for example. these active genetic tools to understand the origins of mammalian diversity. "

The study is published in the journal Nature.

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