Chinese scientists have successfully recombined a mouse’s chromosomes to create the world’s first mammal with fully reprogrammed genes.
Using the gene-editing tool CRISPR, researchers from the Chinese Academy of Sciences (CAS) in Beijing broke down the chromosomes into different segments and rearranged them in different combinations to create a new package of genes, resulting in the mouse called “Xiao Zhu” (Little Bamboo). The paper, published in the academic journal Science on Thursday, revealed that the research team accomplished the first-ever modification of genes in mammals on a scale big as chromosomes.
Chromosomes, which hold DNA in a cell’s nuclei, break apart and recombine naturally via a complicated and delicate process. In the past, humans have only succeeded in replicating the process in a lab with single-cell organisms like yeast.
“Mammalian genomes are much more complex than yeast genomes, and complete chromosomal rearrangements in mammals have remained unsuccessful,” Li Wei, study lead author and Institute of Zoology researcher at the Chinese Academy of Sciences, was quoted as saying.
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Errors during such separation and fusion of chromosomes in natural conditions occasionally result in cancer and other serious conditions.
When Li and his colleagues manipulated the chromosomes by stitching together two very long pieces of a chromosome, they also made some mistakes that resulted in either death in the produced mice or specimens with deformities or weird behaviors.
Using shorter chromosomes and reducing the total number of chromosomes from 20 pairs to 19 enabled them to create a new karyotype in mice that appeared healthy and normal despite having completely different chromosomes from mice in nature.
“For the first time in the world, we have achieved complete chromosomal rearrangement in mammals, making a new breakthrough in synthetic biology,” Li was quoted as saying. “This research is a breakthrough in bioengineering technology, helping to understand the impact of large-scale remodeling of mammalian chromosomes, and to gain a deeper understanding of the molecular mechanisms behind growth and development, reproductive evolution, and even the creation of a species.”
The reprogrammed mice were able to mate and bear offspring with normal mice, suggesting that artificial changes can be passed through generations.
The mice, however, reproduced at a much lower rate than standard lab mice due to an abnormality in how chromosomes separated after alignment.
According to the scientists, their breakthrough could potentially lead to cures for conditions such as infertility and diseases like cancer, as it allows researchers to observe and control the chromosomes in the cells of mammals.
In 2018, Southern University of Science and Technology of China (SUSTC) Associate Professor He Jiankui drew near-universal criticism for creating the world’s first gene-edited babies using CRISPR. He was released from prison in April this year after being sentenced in January 2020 for deliberately violating China’s biomedical regulations.