Cas9 Gene Drive & Classical Biological Control

An example of classical biological control

Webber et al have published an Opinion essay in PNAS concerning the growing interest in using engineered endonucleases (Cas9 in particular) to create gene drive systems to combat invasive species.

Homing endonucleases are well known and well studied site-specific endonucleases that can drive through populations under some conditions and current gene editing systems and the Cas9 system in particular can be configured to behave in exactly the same way. That the Cas9 system can be tuned or engineered to recognize a large number of target sites in potentially any genome means that gene drive systems which have been of great interest to insect biologists since the 1960’s as potential tools for dealing with pest populations are now essentially freely available.

HEG Drive

Site specific endonucleases, like homing endonucleases or engineered endonucleases like Cas9, ZFNs and TALENs can drive through populations by promoting their duplication within the host genome.

Drive systems can now be created that can lead to the extinction of invasive species with seemingly little effort.  A magic bullet or threat to global conservation?

Webber et al discuss gene drive in a broader context not limited to invasive insect pests but any invasive species.

The authors consider the implications of this new found capability to willfully drive extinctions through the lens of classical biological control which they argue has much to teach us about how we might proceed.

In classical biological control, according to the authors, three major considerations are made: 1) understanding target specificity, 2) population connectivity and its implications, and (iii) unintended cascades for community dynamics.

A recent scheme showing the consequences of distorting mosquito sex ratios using a "precision" drive system.

A recent scheme showing the consequences of distorting mosquito sex ratios using a “precision” drive system.

The authors’ discussion is cogent and interesting and part of a much larger ongoing conversation about engineered endonuclease-based gene drive systems.

In the authors’ own words:

“We contend that the extensive experience of regulatory successes (and failures) in the context of CBC can offer an existing framework to provide meaningful guidance for assessing risks and benefits for applications related to invasive species control within this emerging field. The time to develop this regulatory framework is now. “

This short essay is worth reading and the idea that contemporary approaches to classical biological control should be leveraged against the challenges of developing and deploying new synthetic gene drive systems with potential to drive local populations or even entire species to extinction is worth thinking about.

Webber, B.L, Raghu, S. and Edwards, R. (2015) Opinion: Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat? PNAS Early Edition www.pnas.org/cgi/doi/10.1073/pnas.1514258112

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