Developing gene drive technologies to eradicate invasive rodents from islands

Figures & data

Figure 1. Sry gene drive: to skew sex ratios in naturally breeding populations, the male determining gene (Sry), normally found on chromosome (Chr) Y, can be inserted into a naturally occurring gene drive element on Chr 17 called the t-complex. The t-complex is passed down to greater than 90% of the offspring through the paternal side. XX and XY indicate the sex chromosomes and A indicates any of the 22 autosomes. A_Sry is the Sry gene inserted into an autosome and A^t_Sry is Sry inserted into the t complex. (A) In normal breeding scenarios, the Sry gene is only located on Chr Y and therefore only mice inheriting Chr Y are male, resulting in approximately 50% of the offspring are XY (male) and 50% are XX (female). (B) In a breeding scenario where the Sry gene has been added to any autosome, approximately 75% of the offspring will be male and 25% will be female. (C) In breeding scenarios where the male carries the Sry gene within the t-complex, over 90% of offspring will inherit the t-complex containing autosome. It is predicted that fewer than 10% of the offspring will be XX (female), with the remaining being phenotypically male, including either XY (male) or XX (sterile male).

Table 1. Comparing toxicants and gene drives.

Method	Function	Effectiveness	Cost (US dollars)	Pros	Cons	Containment and reversal
Toxicants	Primarily Brodifacoum. Ingested toxicant causes internal hemorrhaging^h	5–10% failure rates for rats, up to 60% failure rate for mice^a^,g	Millions of dollars per island^f	− Established protocol^g − High success rate for rats^g	− Inhumane^c − Secondary effects for endemic species^g − Not suitable for use around humans^c − Not as effective for mice^a − High fixed costs^f	− Geographical containment − Toxicant degrades over time^h − Only reversal is to re-introduce invasive rodents to the system
Gene Drives	Using either the t-haplotype (mice) or CRISPR (mice and rats) to ensure all offspring are phenotypically male (Figure 1)	Unknown – modeling predicts high success potential if minimum release rate is surpassed^b	Millions of dollars to develop, likely to decrease over time^d	− Species-specific^e biologically safe to use around humans − Non-lethal method^c	− Social acceptability unknown − Questions of containment, especially for CRISPR^e^,^k	− Geographic containment − Threshold dependent^b − Target the engineered sequence and/or release resistant rodents back into population^i,j

Note: Though much of what is known regarding the implementation of gene drives in an invasive rodent context is hypothetical, comparisons with toxicants are possible on many key points. This table summarizes the primary points for how each technology works, its cost, how effective it is, its advantages and disadvantages, and whether or not the technology can be contained or reversed.

^aAngel, Wanless, and Cooper (2009).

^bBackus and Gross (2016).

^cCampbell et al. (2015).

^dBackus et al. (2016).

^eEsvelt et al. (2014).

^fHolmes et al. (2015).

^gHowald et al. (2007).

^hIshizuka et al. (2008).

ⁱManser, König, and Lindholm (2015).

^jMin, Smidler, and Esvelt (Forthcoming).

^kNASEM (2016).

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