Resistance to natural and synthetic gene drive systems

Gene drive is a naturally occurring phenomenon in which selfish genetic elements manipulate gametogenesis and reproduction to increase their own transmission to the next generation. Currently, there is great excitement about the potential of harnessing such systems to control major pest and vector populations. If synthetic gene drive systems can be constructed and applied to key species, they may be able to rapidly spread either modifying or eliminating the targeted populations. This approach has been lauded as a revolutionary and efficient mechanism to control insect-borne diseases and crop pests. Driving endosymbionts have already been deployed to combat the transmission of dengue and Zika virus in mosquitoes. However, there are a variety of barriers to successfully implementing gene drive techniques in wild populations. There is a risk that targeted organisms will rapidly evolve an ability to suppress the synthetic drive system, rendering it ineffective. There are also potential risks of synthetic gene drivers invading non-target species or populations. This Special Feature covers the current state of affairs regarding both natural and synthetic gene drive systems with the aim to identify knowledge gaps. By understanding how natural drive systems spread through populations, we may be able to better predict the outcomes of synthetic drive release.

Anticipatory governance of gene drive systems

10.1603/ice.2016.92368 ◽

2016 ◽

Author(s):

Jennifer Kuzma

Keyword(s):

Gene Drive ◽

Anticipatory Governance ◽

Drive Systems

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

10.1101/2021.02.10.430702 ◽

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.

Containment strategies for synthetic gene drive organisms and impacts on gene flow.

10.1079/9781789247480.0010 ◽

2021 ◽

pp. 137-152

Author(s):

Lei Pei ◽

Markus Schmidt

Keyword(s):

Gene Flow ◽

Fungal Infections ◽

Basic Research ◽

Fruit Fly ◽

Mitigation Strategies ◽

Synthetic Gene ◽

Model Organisms ◽

Gene Drive ◽

Comprehensive Overview ◽

Gene Drives

Abstract Gene drives, particularly synthetic gene drives, may help to address some important challenges, by efficiently altering specific sections of DNA in entire populations of wild organisms. Here we review the current development of the synthetic gene drives, especially those RNA-guided synthetic gene drives based on the CRISPR nuclease Cas. Particular focuses are on their possible applications in agriculture (e.g. disease resistance, weed control management), ecosystem conservation (e.g. evasion species control), health (e.g. to combat insect-borne and fungal infections), and for basic research in model organisms (e.g. Saccharomyces, fruit fly, and zebra fish). The physical, chemical, biological, and ecological containment strategies that might help to confine these gene drive-modified organisms are then explored. The gene flow issues, those from gene drive-derived organisms to the environment, are discussed, while possible mitigation strategies for gene drive research are explored. Last but not least, the regulatory context and opinions from key stakeholders (regulators, scientists, and concerned organizations) are reviewed, aiming to provide a more comprehensive overview of the field.

Gene Therapy: A Promising Therapeutic Strategy for Malaria

University of Ottawa Journal of Medicine ◽

10.18192/uojm.v8i2.3651 ◽

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.