The & # 39; allelic disc & # 39; based on CRISPR allows genetic editing with selective precision and broad implications

The & # 39; allelic disc & # 39; based on CRISPR allows genetic editing with selective precision and broad implications

The & # 39; allelic disc & # 39; based on CRISPR allows genetic editing with selective precision and broad implications



The next generation gene arrives

The gene unit is mediated by an RNA guide (RNAg) that cuts at the exact site (scissors) where the gene unit element (blue box: Cas9 gene; yellow box: mRNA) is inserted into the genome, which results in a unit of copy of elements. Right panel: the new allelic unit is achieved by the addition of a second gRNA (blue box) to a gene unit element that preferentially cuts a damaging allele (scissors), but not the beneficial allele, resulting in an allelic copy beneficial Credit: Bier Lab, UC San Diego

The new genetic units based on CRISPR and the broader active genetic technologies are revolutionizing the way scientists design the transfer of specific traits from one generation to another.

Scientists at the University of California at San Diego have now developed a new version of a genetic unit that opens the door to the spread of favorable, specific, subtle genetic variants, also known as "alleles," throughout the population.

The new "allelic impulse", described on April 9 in Communications of nature, is equipped with an RNA guide (RNAg) that directs the CRISPR system to cut unwanted variants of a gene and replace it with a preferred version of the gene. The new unit expands the ability of scientists to modify populations of organisms with precision editing. By using word processing as an badogy, CRISPR-based genetic units allow scientists to edit sentences of genetic information, while the new allele unit offers letter-for-letter editing.

In one example of their potential applications, specific genes in agricultural pests that have become resistant to insecticides could be replaced by original natural genetic variants that confer sensitivity to insecticides using allelic units that selectively exchange the identities of a single protein residue. (amino acid)

In addition to agricultural applications, insect-carrying diseases could be a target for allelic units.

"If we incorporate a gRNA that is normalized into a genetic element, for example, one designed to immunize mosquitoes against malaria, the resulting allelic gene unit will propagate through a population. insecticide-resistant allele, will cut it and repair it using the wild-type susceptible allele, "said Ethan Bier, the lead author of the new article. "The result is that almost all the emerging progeny will be sensitive to insecticides, as well as malaria transmission."

The next generation gene arrives

The gene unit is mediated by an RNA guide (RNAg) that cuts at the exact site (scissors) where the gene unit element (blue box: Cas9 gene; yellow box: mRNA) is inserted into the genome, which results in a unit of copy of elements. Right panel: the new allelic unit is achieved by the addition of a second gRNA (blue box) to a gene unit element that preferentially cuts a damaging allele (scissors), but not the beneficial allele, resulting in an allelic copy beneficial Credit: Bier Lab, UC San Diego

"Forcing these species to return to their sensitive natural state through the use of allelic units would help to break a down cycle of pesticide overuse that is increasingly damaging to the environment," said Annabel Guichard, the first author of the article.

The researchers describe two versions of the allelic unit, including "copying," in which researchers use the CRISPR system to selectively cut the unwanted version of a gene, and a broader application version called "copying" that promotes transmission. of a favored allele next to the site that is selectively protected from the excision of the gRNA.

"An unexpected finding of this study is that the errors created by such allelic units are not transmitted to the next generation," said Guichard. "These mutations instead produce an unusual form of lethality known as" lethal mosaicism. "This process helps make allelic units more efficient by immediately eliminating unwanted mutations created by CRISPR-based units.

Although proven in fruit flies, the new technology also has potential for widespread application in insects, mammals and plants. According to the researchers, several variations of allelic drive technology could be developed with combinations of favorable traits in crops that, for example, thrive in poor soils and arid environments to help feed the ever-growing world population.

Beyond environmental applications, allelic units must allow the engineering of next-generation animal models to study human diseases, as well as answer important questions in basic science. As a member of the Tata Institute of Genetics and Society (TIGS), Bier says that allelic drives could be used to help environmental conservation efforts to protect vulnerable endemics or stop the spread of invasive species.

Genetic drivers and active genetics systems are being developed for use in mammals. Scientists say that allelic drives could accelerate new laboratory strains of animal models of human diseases that help in the development of new cures.


Maintain localized genetic engineering.


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University of California – San Diego


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The & # 39; allelic disc & # 39; based on CRISPR allows genetic editing with selective precision and broad implications (2019, April 10)
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