Cleave and Rescue, a novel selfish genetic element and general strategy for gene drive

Georg Oberhofer, Tobin Ivy, Bruce A. Hay

Proceedings of the National Academy of Sciences · 2019 · 192 citations · 64 references

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Concepts

TL;DR

There is great interest in spreading beneficial traits throughout wild populations in self‑sustaining ways. Here, we describe a synthetic selfish genetic element, CleaveR (ClvR), that is simple to build and can spread a linked gene to high frequency in populations. ClvR consists of germline‑expressed Cas9/gRNAs that cleave an essential gene and a resistant copy that restores function, so individuals lacking ClvR die while carriers survive, driving the element to high frequency.

Abstract

Significance There is great interest in spreading beneficial traits throughout wild populations in self-sustaining ways. Here, we describe a synthetic selfish genetic element, CleaveR [Cleave and Rescue ( ClvR )], that is simple to build and can spread a linked gene to high frequency in populations. ClvR is composed of two components. The first, germline-expressed Cas9 and guide RNAs (gRNAs), cleave and disrupt versions of an essential gene located elsewhere in the genome. The second, a version of the essential gene resistant to cleavage, provides essential gene function. ClvR spreads by creating conditions in which progeny lacking ClvR die because they have no functional copies of the essential gene. In contrast, those who inherit ClvR survive, resulting in an increase in ClvR frequency.

References

64