Evaluating the Probability of CRISPR-based Gene Drive Contaminating Another Species

Abstract

The probability D that a given CRISPR-based gene drive element contaminates another, non-target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation:

• D = (hyb+transf).express.cut.flank.immune.nonextinct with

• hyb = probability of hybridization between the target species and a non-target species

• transf = probability of horizontal transfer of a piece of DNA containing the gene drive cassette from the target species to a non-target species (with no hybridization)

• express = probability that the Cas9 and guide RNA genes are expressed

• cut = probability that the CRISPR-guide RNA recognizes and cuts at a DNA site in the new host

• flank = probability that the gene drive cassette inserts at the cut site

• immune = probability that the immune system does not reject Cas9-expressing cells

• nonextinct = probability of invasion of the drive within the population

We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans. We conclude from current data that the probability of a gene drive cassette to contaminate another species is not insignificant. We propose strategies to reduce this risk and call for more work on estimating all the parameters of the formula.