CRISPR-based ‘allelic drive’ allows genetic editing with selective precision and broad implications
New CRISPR-based gene drives and broader active genetics technologies are revolutionizing the way scientists engineer the transfer of specific traits from one generation to another.
Scientists at the University of California San Diego have now developed a new version of a gene drive that opens the door to the spread of specific, favorable subtle genetic variants, also known as “alleles,” throughout a population.
The new “allelic drive,” described April 9 in Nature Communications, is equipped with a guide RNA (gRNA) that directs the CRISPR system to cut undesired variants of a gene and replace them with a preferred version of the gene. The new drive extends scientists’ ability to modify populations of organisms with precision editing. Using word processing as an analogy, CRISPR-based gene drives allow scientists to edit sentences of genetic information, while the new allelic drive offers letter-by-letter editing.
In one example of its potential applications, specific genes in agricultural pests that have become resistant to insecticides could be replaced by original natural genetic variants conferring sensitivity to insecticides using allelic drives that selectively swap the identities of a single protein residue (amino acid).
In addition to agricultural applications, disease-carrying insects could be a target for allelic drives.
“If we incorporate such a normalizing gRNA on a gene-drive element, for example, one designed to immunize mosquitoes against malaria, the resulting allelic gene drive will spread through a population. When this dual action drive encounters an insecticide-resistant allele, it will cut and repair it using the wild-type susceptible allele,” said Ethan Bier, the new paper’s senior author. “The result being that nearly all emerging progeny will be sensitive to insecticides as well as refractory to malaria transmission.”
“Forcing these species to return to their natural sensitive state using allelic drives would help break a downward cycle of ever-increasing and environmentally damaging pesticide over-use,” said Annabel Guichard, the paper’s first author.
The researchers describe two versions of the allelic drive, including “copy-cutting,” in which researchers use the CRISPR system to selectively cut the undesired version of a gene, and a more broadly applicable version referred to as “copy-grafting” that promotes transmission of a favored allele next to the site that is selectively protected from gRNA cleavage.
“An unexpected finding from this study is that mistakes created by such allelic drives do not get transmitted to the next generation,” said Guichard. “These mutations instead produce an unusual form of lethality referred to as ‘lethal mosaicism.’ This process helps make allelic drives more efficient by immediately eliminating unwanted mutations created by CRISPR-based drives.”
Although demonstrated in fruit flies, the new technology also has potential for broad application in insects, mammals and plants. According to the researchers, several variations of the allelic drive technology could be developed with combinations of favorable traits in crops that, for example, thrive in poor soil and arid environments to help feed the ever-growing world population.
Beyond environmental applications, allelic drives should enable next-generation engineering of animal models to study human disease as well as answer important questions in basic science. As a member of the Tata Institute for Genetics and Society (TIGS), Bier says allelic drives could be used to aid in environmental conservation efforts to protect vulnerable endemic species or stop the spread of invasive species.
Gene drives and active genetics systems are now being developed for use in mammals. The scientists say allelic drives could accelerate new laboratory strains of animal models of human disease that aid in the development of new cures.
Learn more: Next-generation Gene Drive Arrives
The Latest on: Allelic drive
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The Latest on: Allelic drive
- Gene Drive Modified to Run Allelic Errands on April 10, 2019 at 7:40 am
A new gene drive system introduces gears well suited to the transmission of relatively slight genetic variants, that is, allelic variants involving only one or a few base pairs. Typical gene drive ... […]
- CRISPR-based 'allelic drive' allows genetic editing with selective precision and broad implications on April 10, 2019 at 6:32 am
Scientists developed a new version of a gene drive that allows the spread of specific, favorable genetic variants, also known as 'alleles,' throughout a population. The new 'allelic drive' is equipped ... […]
- New “Allelic” Gene Drive Replaces Faulty Genes with Preferred Versions on April 10, 2019 at 6:15 am
Scientists at the University of California San Diego have created a new version of a gene drive which could lead to spreading specific, favourable genetic variants through a population. This “allelic ... […]
- CRISPR-based 'allelic drive' allows genetic editing with selective precision and broad implications on April 9, 2019 at 11:51 pm
New CRISPR-based gene drives and broader active genetics technologies are revolutionizing the way scientists engineer the transfer of specific traits from one generation to another. Scientists at ... […]
- Scientists develop new CRISPR-based 'allelic drive' on April 9, 2019 at 9:25 pm
New CRISPR-based gene drives and broader active genetics technologies are revolutionizing the way scientists engineer the transfer of specific traits from one generation to another. Scientists at the ... […]
- Next-generation Gene Drive Arrives on April 9, 2019 at 5:57 pm
Right panel: The new allelic drive is accomplished by the addition of a second gRNA (blue box) to a gene drive element that preferentially cuts a detrimental allele (scissors), but not the beneficial ... […]
- Gene-Drive Versus Allelic Drive (image) on April 9, 2019 at 2:02 pm
Gene-drive is mediated by a guide RNA (gRNA) that cuts at the exact site (scissors) where the gene-drive element (blue box: Cas9 gene; yellow box: gRNA) is inserted into the genome, resulting in full ... […]
- Efficient allelic-drive in Drosophila on April 9, 2019 at 2:15 am
Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. Here, we generalize this “active genetic” approach to preferentially transmit allelic ... […]
- Allelic frequencies of host genetic variants influencing susceptibility to HIV-1 infection and disease in South African populations on March 9, 2019 at 4:00 pm
The objective of this study was to determine the allelic frequencies in South African populations ... Requests for reprints to: Dr C. Williamson, SAIMR Virology, Department of Medical Microbiology, ... […]
- Allelic polymorphism and complexity of the genes for HLA-DR β-chains—direct analysis by DNA–DNA hybridization on February 21, 2019 at 3:38 am
HLA-DR antigens are highly polymorphic cell surface glyco-proteins involved in the control of the immune response. They are important in allograft rejection and in their linkage to certain disease ... […]
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