The Road Ahead for Using Gene Drive Systems

Emerging technologies have employed chemical, ecological and genetic strategies for effective and economical pest management. The various strategies around the transgenic augmentation of pests has shown great promise in being able to combat vector borne diseases and eradicate agricultural pests in the lab, however, implementing these strategies into the environment encounters a common speed bump: Mendelian genetics.

In organisms that reproduce sexually there is an average 50% chance of inheriting an altered gene leading to its integration into a population over many generations. Depending on the organism the generation time could be anywhere from months to centuries; in the latter case, too long to be considered for control through gene augmentation. So, how can researchers implement transgenic based strategies at speeds that can lead to applicable solutions?

In this recent Sciencexpress publication, Oye, (2014) address the current status of the gene drive field and how they might be moved forward for addressing various practical problems.  This paper is a by-product of two workshops on “Creating a research agenda for the ecological implications of synthetic biology” held at MIT on 8 and 9 January 2014 and at the University of California at Berkeley on 16 and 17 January 2014.

Natural gene drive systems, for example meiotic drive (a term first used by Sandler and Novitski in 1957), have been studied in insects since the late 1950’s.  George Craig investigated various systems in mosquitoes and suggested that they might be useful for genetic control (see Craig 1960)

“Synthetic” Gene drive systems have been previously investigated and have consisted of  transposable elements, toxin-antidote expression systems (MEDEA), etc, as their mode of action. Here, the authors address another class of gene drive system based on targeted endonuclease enzymes.

CRISPR/Cas9 Knock-in Technology could be used as a genetic drive system to 'spread' genes through natural populations.

CRISPR/Cas9 Knock-in Technology could be used as a genetic drive system to ‘spread’ genes through natural populations.

The “hot” CRISPR/Cas9 system makes an appearance, yet again, as a means for targeting a site of DNA cleavage and potentially DNA insertion.  A germline system would be continually active and would insure 100% homozygosity for either a cleaved and imperfectly repaired target gene or a transgene insertion. These “precision” drives could be maintained in organisms in nature so long as they were routinely updated and have limited off-target effects.

There was a recent description of a real, working drive system in mosquitoes that put the ideas of Oye et al into practice.  The system reported could be used to locally eradicate the human malaria mosquito, Anopheles gambiaeSee the IGTRCN’s recent blog about this.

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.

In addition to the practical applications for a targeted endonuclease gene drive system the authors also point some attention towards two other areas that have been underdeveloped: risk management and regulation. In a ten-point section, the authors outline points for researchers to consider when planning gene drive systems for release. The authors also direct attention to how gene drive systems are currently defined by US and international policies. Particular renovation will be required in the area of policy to ensure that “good science” is disseminated to the public in an informed manner.

Again, the insect community has been thinking about these issues for quite some time and some of this thinking is reflected in a recent guidance document published by the World Health Organization intended to serve to guide the release of transgenic mosquitoes.  The document looks in detail at the ideas outlined by Oye et al. (2014)Go here to see the IGTRCN’s recently posted a blog about the WHO guidance document.

New tools for gene drive systems exist that can lead to relatively safe and effective gene replacement, augmentation, or integration. It appears as the technologies keep advancing the policies and strategies for implementation are going to have to speed up to allow researchers the opportunity to make solutions a reality.

Sandler, L and E. Novitski  1957 Meiotic drive as an evolutionary force. Am. Naturalist 91:105-110

Craig Jr., George B. 1967 Genetic Control of Aedes aegypti  Bull. Wld Hlth Org 36 628-632

Regulating gene drives. Kenneth A. Oye, Kevin Esvelt, Evan Appleton, Flaminia Catteruccia, George Church, Todd Kuiken, Shlomiya Bar-Yam Lightfoot, Julie McNamara, Andrea Smidler, and James P. Collins. Science 1254287Published online 17 July 2014 [DOI:10.1126/science.1254287]




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