scholarly journals Can CRISPR-based gene drive be confined in the wild? A question for molecular and population biology

2017 ◽  
Author(s):  
John M. Marshall ◽  
Omar S. Akbari
Keyword(s):  
Population Biology ◽  
Gene Editing ◽  
Gene Drive ◽  
In The Wild ◽  
Drive Systems ◽  
Chain Drives

AbstractThe recent discovery of CRISPR and its application as a gene editing tool has enabled a range of gene drive systems to be engineered with much greater ease. In order for the benefits of this technology to be realized, drive systems must be developed that are capable of both spreading into populations to achieve their desired impact, and being recalled in the event of unwanted consequences or public disfavor. We review the performance of three broad categories of drive systems at achieving these goals - threshold-dependent drives, homing-based drive and remediation systems, and temporally self-limiting systems such as daisy-chain drives.

scholarly journals Fitness consequences of a non-recombining sex-ratio drive chromosome can explain its prevalence in the wild

2019 ◽  
Vol 286 (1917) ◽  
pp. 20192529 ◽  
Author(s):  
Kelly A. Dyer ◽  
David W. Hall
Keyword(s):  
Sex Ratio ◽  
Sperm Competition ◽  
Natural Populations ◽  
Theoretical Models ◽  
Host Population ◽  
Gene Drive ◽  
Fitness Consequences ◽  
In The Wild ◽  
And Performance ◽  
Drive Systems

Understanding the pleiotropic consequences of gene drive systems on host fitness is essential to predict their spread through a host population. Here, we study sex-ratio (SR) X-chromosome drive in the fly Drosophila recens , where SR causes the death of Y-bearing sperm in male carriers. SR males only sire daughters, which all carry SR, thus giving the chromosome a transmission advantage. The prevalence of the SR chromosome appears stable, suggesting pleiotropic costs. It was previously shown that females homozygous for SR are sterile, and here, we test for additional fitness costs of SR. We found that females heterozygous for SR have reduced fecundity and that male SR carriers have reduced fertility in conditions of sperm competition. We then use our fitness estimates to parametrize theoretical models of SR drive and show that the decrease in fecundity and sperm competition performance can account for the observed prevalence of SR in natural populations. In addition, we found that the expected equilibrium frequency of the SR chromosome is particularly sensitive to the degree of multiple mating and performance in sperm competition. Together, our data suggest that the mating system of the organism should be carefully considered during the development of gene drive systems.

scholarly journals Retargeting: an unrecognized consideration in endonuclease-based gene drive biology

2016 ◽  
Author(s):  
Andrew M. Scharenberg ◽  
Barry L Stoddard ◽  
Raymond J Monnat ◽  
Anthony Nolan
Keyword(s):  
Gene Editing ◽  
Insect Pests ◽  
Field Testing ◽  
Nuclease Activity ◽  
Genome Replication ◽  
Gene Drive ◽  
Regulatory Issues ◽  
Guide Rna ◽  
Insect Populations ◽  
Drive Systems

AbstractThere is intense interest surrounding the use of gene editing nucleases in gene drive systems to control agricultural insect pests and insect vectors of infectious diseases such as malaria, dengue and Zika virus. While gene drive systems offer immense promise for the beneficial modification of deleterious insect populations, their unique mechanism of action also raises novel safety concerns and regulatory issues. A recent US National Academies of Science report provides a list of potential regulatory issues associated with implementation of homologous recombination (HR)-mediated gene drive systems, based on the premise that all such systems would exhibit similar biological behaviors. Here we examine how HR-mediated gene drive systems based on different gene editing nuclease platforms could be affected by mutations that occur during host cell transcription, genome replication, and, in conjunction with gene editing nuclease activity, during HR-mediated gene drive. Our analysis suggests that the same feature that makes RNA-guided nucleases such attractive research tools—their ease of reprogramming by alterations to their guide RNA components—might also contribute to increased rates of retargeting that could influence the long term behavior of RNA-guided gene drive systems. Predictability of behavior over time is an issue that should be addressed by in-depth risk assessment before field testing of organisms incorporating nuclease-mediated gene drives.

scholarly journals Optimized CRISPR tools and site-directed transgenesis in Culex quinquefasciatus mosquitoes for gene drive development

2021 ◽  
Author(s):  
Xuechun Feng ◽  
Víctor López Del Amo ◽  
Enzo Mameli ◽  
Megan Lee ◽  
Alena L. Bishop ◽  
...  
Keyword(s):  
Culex Quinquefasciatus ◽  
Technology Development ◽  
Companion Animals ◽  
Fruit Fly ◽  
Valuable Insight ◽  
Gene Drive ◽  
Future Technology ◽  
Drive Systems ◽  
Global Vector ◽  
Human And Animal Diseases

ABSTRACTCulex mosquitoes are a global vector for multiple human and animal diseases, including West Nile virus, lymphatic filariasis, and avian malaria, posing a constant threat to public health, livestock, companion animals, and endangered birds. While rising insecticide resistance has threatened the control of Culex mosquitoes, advances in CRISPR genome-editing tools have fostered the development of alternative genetic strategies such as gene drive systems to fight disease vectors. However, though gene-drive technology has quickly progressed in other mosquitoes, advances have been lacking in Culex. Here, we developed a Culex-specific Cas9/gRNA expression toolkit and used site-directed homology-based transgenesis to generate and validate a Culex quinquefasciatus Cas9-expressing line. We showed that gRNA scaffold variants improve transgenesis efficiency in both Culex and Drosophila and boost gene-drive performance in the fruit fly. These findings support future technology development to control Culex mosquitoes and provide valuable insight for improving these tools in other species.

scholarly journals The Decision Phases Framework for Public Engagement: Engaging Stakeholders about Gene Editing in the Wild

2021 ◽  
Vol 51 (S2) ◽  
Author(s):  
S. Kathleen Barnhill‐Dilling ◽  
Adam Kokotovich ◽  
Jason A. Delborne
Keyword(s):  
Public Engagement ◽  
Gene Editing ◽  
In The Wild

scholarly journals Gene Editing in the Wild: Who Decides—and How?

BioScience ◽  
2019 ◽  
Vol 69 (4) ◽  
pp. 316-316
Author(s):  
Niki Wilson
Keyword(s):  
Gene Editing ◽  
In The Wild

scholarly journals Gene Therapy: A Promising Therapeutic Strategy for Malaria

2018 ◽  
Vol 8 (2) ◽  
pp. 40-44
Author(s):  
Raafay Shehzad
Keyword(s):  
Gene Therapy ◽  
Therapeutic Strategy ◽  
Homing Endonuclease ◽  
Genetic Material ◽  
Gene Drive ◽  
Treatment And Prevention ◽  
Preventative Measures ◽  
Drive Systems ◽  
Embryonic Arrest ◽  
Diabetes And Obesity

Malaria is a serious illness caused by the Plasmodium parasite, which places approximately 3.5 billion people at risk. Currently, preventative measures are key in combatting this disease. However, gene therapy is an emerging field that shows promising results for the treatment of malaria, by modifying cells through the delivery of genetic material. Most notable was the discovery of CRISPR-Cas9, which not only allows deleterious mutations to be repaired, but does so with specificity, speed, and simplicity. There are numerous ongoing trials focusing on gene therapy in malaria treatment and prevention. They involve different approaches such as the genetic modification of vector mosquitoes to interfere with malaria transmission, use of CRISPR-Cas9, maternal-effect dominant embryonic arrest, homing endonuclease gene drive systems, and the design of specific Morpholino oligomers to interfere with the expression of parasitic characteristics. Overall, this emerging field shows promising results to treat and prevent not just malaria, but other diseases such as cancer, diabetes, and obesity.

scholarly journals Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

2020 ◽  
Author(s):  
Adriana Adolfi ◽  
Valentino M. Gantz ◽  
Nijole Jasinskiene ◽  
Hsu-Feng Lee ◽  
Kristy Hwang ◽  
...  
Keyword(s):  
Anopheles Stephensi ◽  
Pathogen Transmission ◽  
Gene Drive ◽  
Initial Release ◽  
Genetic Technologies ◽  
Rescue System ◽  
Vector Borne ◽  
Kynurenine Hydroxylase ◽  
Drive Systems ◽  
Population Suppression

ABSTRACTThe development of Cas9/gRNA-mediated gene-drive systems has bolstered the advancement of genetic technologies for controlling vector-borne pathogen transmission. These include population suppression approaches, genetic analogs of insecticidal techniques that reduce the number of vector insects, and population modification (replacement/alteration) approaches, which interfere with competence to transmit pathogens. We developed a recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion. Small cage trials show that single releases of gene-drive males robustly result in efficient population modification with ≥95% of mosquitoes carrying the drive within 5-11 generations over a range of initial release ratios.

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