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
via Google News
The Latest on: Allelic drive
- Dr Helen Hippersonon September 27, 2020 at 12:58 am
I am a molecular ecologist with a general interest in using molecular techniques to answer questions in ecology, evolution and conservation. My previous research focused on the genetic basis of ...
- Common genetic variants may influence susceptibility to COVID-19on September 22, 2020 at 10:26 pm
The team found that allelic conversion at the common variant rs4702 impacted SARS-CoV-2 infection in human neurons and alveolar cells in vitro. Kristen Brennand (Icahn School of Medicine at Mount ...
- Improved CRISPR-Cas9 delivery method allows for fast and precise knockoutson September 21, 2020 at 9:26 am
Principal investigator Dr. Patrick Paddison explained how this technique could ... A simple and highly efficient method for multi-allelic CRISPR-Cas9 editing in primary cell cultures. Cancer reports ...
- Speaking the Language of Genetics: A Primeron September 19, 2020 at 5:00 pm
Dr. Speer is a genetic epidemiologist and is ... For example, A and B are specific alleles at the ABO blood group gene. Allelic variants can be conceptualized as just another type of biologic ...
- Evaluation of Ultra-deep Targeted Sequencing for Personalized Breast Cancer Careon September 19, 2020 at 5:00 pm
a Depth, accurate calls at low allelic fraction (
- Biologists create new genetic systems to neutralize gene driveson September 18, 2020 at 10:03 am
Addressing concerns about gene drive releases in the wild, scientists have developed two new genetic systems that halt or eliminate gene drives after release. Created in fruit flies, the e-CHACRs ...
- The GTEx Consortium atlas of genetic regulatory effects across human tissueson September 11, 2020 at 4:41 am
We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying ...
- Timothy Rebbeckon August 16, 2020 at 7:57 am
understand the relationship of allelic variation with biochemical or physiological traits, explore interactions of inherited and somatic genomic variation with epidemiological risk factors. Dr.
- The use of massively parallel sequencing in Forensic DNA typing - what will the future hold?on August 10, 2020 at 12:29 am
Dr. Nicole Novroski is an Assistant Professor and Forensic Geneticist ... genetic variation but equally as well inter-allelic sequence (sequence-based; SB) variation. The increased effective number of ...
- Fairy tale ending? Identical strangers who are twin sisterson June 16, 2019 at 2:53 am
“Sharon Mitekwa and Melon Lutenyo share identical DNA profiles, with the 23 allelic loci tested showing ... Completely identical.” As Dr Ahmed Kalebi from Lancet read the results, Mevies ...
via Bing News