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Front. Genet. | doi: 10.3389/fgene.2019.01072

Winning the tug-of-war between effector gene design and pathogen evolution in vector population replacement strategies

  • 1University of California, San Diego, United States
  • 2University of California, Berkeley, United States

While efforts to control malaria with available tools have stagnated, and arbovirus outbreaks persist around the globe, the advent of CRISPR-based gene editing has provided exciting new opportunities for genetics-based strategies to control these diseases. In one such strategy, called “population replacement”, mosquitoes and other disease vectors are engineered with effector genes that render them unable to transmit pathogens. These effector genes can be linked to “gene drive” systems that can bias inheritance in their favor, providing novel opportunities to replace disease-susceptible vector populations with disease-refractory ones over the course of several generations. While promising for the control of vector-borne diseases on a wide scale, this sets up an evolutionary tug-of-war between the introduced effector genes and the pathogen. Here, we review the disease-refractory genes designed to date to target Plasmodium falciparum malaria transmitted by Anopheles gambiae, and arboviruses transmitted by Aedes aegypti, including dengue serotypes 2 and 3, chikungunya and Zika viruses. We discuss resistance concerns for these effector genes, and genetic approaches to prevent parasite and viral escape variants. One general approach is to increase the evolutionary hurdle required for the pathogen to evolve resistance by attacking it at multiple sites in its genome and/or multiple stages of development. Another is to reduce the size of the pathogen population by other means, such as with vector control and antimalarial drugs. We discuss lessons learned from the evolution of resistance to antimalarial and antiviral drugs and implications for the management of resistance after its emergence. Finally, we discuss the target product profile for population replacement strategies for vector-borne disease control. This differs between early phase field trials and wide-scale disease control. In the latter case, the demands on effector gene efficacy are great; however, with new possibilities ushered in by CRISPR-based gene editing, and when combined with surveillance, monitoring and rapid management of pathogen resistance, the odds are increasingly favoring effector genes in the upcoming evolutionary tug-of-war.

Keywords: pathogen, Vector, evolution, Gene drive, Population

Received: 16 May 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Akbari, Marshall, Raban, Kandul, Edula and Leon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Omar Akbari, University of California, San Diego, San Diego, United States, Oakbari@ucsd.edu