Concerning RNA-Guided Gene Drives for the Alteration of Wild Populations

Abstract

Gene drives may be capable of addressing ecological problems by altering entire populations of wild organisms, but their use has remained largely theoretical due to technical constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR nuclease Cas9 to serve as a general method for spreading altered traits through wild populations over many generations. We detail likely capabilities, discuss limitations, and provide novel precautionary strategies to control the spread of gene drives and reverse genomic changes. The ability to edit populations of sexual species would offer substantial benefits to humanity and the environment. For example, RNA-guided gene drives could potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species. However, the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application. We call for thoughtful, inclusive, and well-informed public discussions to explore the responsible use of this currently theoretical technology.

Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat?

“…Unlike previous technologies, CRISPR-Cas9 offers simplicity, flexibility, and precision in gene targeting, such that any standard molecular biology laboratory could adopt the technology with little additional specialist equipment or training (7). Perhaps most importantly, CRISPR-Cas9 is efficient and inexpensive compared with all previously proposed gene drive technologies (4).…”

“…When included as part of a gene drive, a CRISPR-Cas9-generated mutation will make copies of itself anywhere the genome sequence is complementary to the gRNA (7), and hence will convert individuals heterozygous for the mutation into homozygotes (4). Unlike previous technologies, CRISPR-Cas9 offers simplicity, flexibility, and precision in gene targeting, such that any standard molecular biology laboratory could adopt the technology with little additional specialist equipment or training (7).…”

“…Biosecurity is just one of many areas in which CRISPR-Cas9 gene drive technology is being focused (4). It is encouraging that momentum is building to engage stakeholders and scientists from various disciplines into a public discussion on the potential applications of gene drives (see dels.nas.edu/StudyIn-Progress/Gene-Drive-Research-Human/ DELS-BLS-15-06).…”

“…Recent developments in clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology have restarted discussions of using gene drive for invasive species control (4).…”

CRISPR gene editing

“…Church and Kevin Esvelt, of Harvard's Wyss Institute for Biologically Inspired Engineering, have suggested that one could use CRISPR/Cas9 to modify an entire population of wild organisms (10). A prime target: mosquitoes that carry pathogens such as the malaria parasite.…”