Cheating evolution: engineering gene drives to manipulate the fate of wild populations

Abstract

Engineered gene drives - the process of stimulating the biased inheritance of specific genes - have the potential to enable the spread of desirable genes throughout wild populations or to suppress harmful species, and may be particularly useful for the control of vector-borne diseases such as malaria. Although several types of selfish genetic elements exist in nature, few have been successfully engineered in the laboratory thus far. With the discovery of RNA-guided CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated 9) nucleases, which can be utilized to create, streamline and improve synthetic gene drives, this is rapidly changing. Here, we discuss the different types of engineered gene drives and their potential applications, as well as current policies regarding the safety and regulation of gene drives for the manipulation of wild populations.

Evolution of Resistance Against CRISPR/Cas9 Gene Drive

“…Thus, even though a driver may initially spread to high frequency in the population, its ultimate fate will depend on whether resistance alleles have emerged during this process. While several strategies have been proposed for reducing resistance potential; including the use of multiple gRNAs, the targeting of essential genes, daisy chains, or poison-antidote systems Champer et al 2016;Noble et al 2016a); it remains to be seen how well these approaches can actually work in practice.It is clear that any informed decision about the potential consequences and risks of releasing a CGD construct into a wild population requires that we first understand the dynamics of this process on the population level, including potential resistance mechanisms. Here, we build on previous theoretical results to devise a comprehensive population genetic model of CGD, which allows us to quantitatively study the population dynamics of such systems, calculate the probability that resistance evolves, and predict how resistance alleles will interfere with the spread of a driver construct.…”

“…Potential applications are broad and ambitious, including the eradication of vectorborne diseases such as malaria, dengue, and Zika (Burt 2003;Esvelt et al 2014;Champer et al 2016). For example, mosquitoes could be genetically altered such that they can no longer transmit Plasmodium parasites.…”

A roadmap for gene drives: using institutional analysis and development to frame research needs and governance in a systems context

“…In this volume, Min et al (2017) describe a technical typology of gene drives and their risks and benefits, extending that of Champer, Buchman, and Akbari (2016) and Sinkins and Gould (2006 with a particular focus on localization and public perception). As described by Champer, Buchman, and Akbari (2016), technological choices include (1) whether the gene drive is designed to suppress the target population or to replace it; (2) the rate of its spread; (3) whether it is locally confined or not; (4) whether it has a fitness cost; (5) the rate of resistance allele generation; (6) whether it is reversible; and (7) whether it can be removed and replaced with the original wild-type individuals.…”

“…In this volume, Min et al (2017) describe a technical typology of gene drives and their risks and benefits, extending that of Champer, Buchman, and Akbari (2016) and Sinkins and Gould (2006 with a particular focus on localization and public perception). As described by Champer, Buchman, and Akbari (2016), technological choices include (1) whether the gene drive is designed to suppress the target population or to replace it; (2) the rate of its spread; (3) whether it is locally confined or not; (4) whether it has a fitness cost; (5) the rate of resistance allele generation; (6) whether it is reversible; and (7) whether it can be removed and replaced with the original wild-type individuals. Other key choices among gene drives were discussed and included whether a given drive system was anticipated to spread to all members of the target population (self-sustaining); whether it was intended to enhance, replace, suppress, or eliminate the population (control system or cargo carried); whether it could be actively eliminated by subsequent releases (reversibility); and whether the drive system required an exogenous factor in order to act (inducibility).…”

Anomaly handling and the politics of gene drives

“…Many scientists working on gene drives are also developing technical modifications to address some of the ways these drives might be perceived as regulatory anomalies. These efforts include work on molecular strategies for biocontainment Akbari et al 2015), reversal and immunization drives (DiCarlo et al 2015;Champer, Buchman, and Akbari 2016), and drives that can be limited to a certain number of generations (Min et al 2017a(Min et al , 2017b. This research agenda has received a notable boost with the development of the DARPA Safe Genes Program.…”