A Framework for the Risk Assessment and Management of Gene Drive Technology in Contained Use

Abstract

The utilisation of the CRISPR/Cas9 technology has sparked a renewed interest in gene drive mechanisms. These mechanisms of biased inheritance may yield promising applications in the fields of vector control and nature conservation. However, the same properties that will enable these applications may also pose a risk if organisms that are equipped with gene drive cassettes are unintentionally released into the environment. Although several groups of scientists and regulators have started to address these safety concerns, there are currently no dedicated guidelines published on the required risk assessment and minimal control measures applicable to gene drive organisms in contained use. To fill this gap, this paper describes a fundamental approach to assessing the risks of these organisms while handled in a contained laboratory environment. Based on the likelihood that an adverse effect will arise from the handling of a gene drive organism and the severity of this effect, three risk classes for contained use activities are presented. Finally, specific minimum requirements regarding physical measures and working practices are proposed according to the presented risk classes and tailored to activities with rodents, insects, and fungi, which are most likely to be used for gene drive applications in the near future.

Population management using gene drive: molecular design, models of spread dynamics and assessment of ecological risks

“…Molecular resistance can occur either through standing genetic variation (i.e. polymorphism at the target site) or through evolution by de novo mutations (Unckless et al 2017).…”

“…In addition, genetic variation in the NHEJ repair system both among and within target populations could select for increased resistance to gene drives (Champer et al 2017(Champer et al , 2018b. Indel mutations conferring resistance are selected for when their fitness costs are lower than the fitness costs associated with gene drive alleles (Unckless et al 2017). Studies suggest that, in plants, NHEJ repair predominates over homology directed repair (Gorbunova and Levy 1999;Li et al 2013).…”

“…The unintentional release of gene drive individuals in the environment can represent an important risk for the safety of humans and their environment. Best practice guidelines have been proposed by various groups of experts (NASEM 2016; Lunshof and Birnbaum 2017; Krishnan and Gillum 2017;van der Vlugt et al 2018). Gene drive strains should be managed using an appropriate combination of confinement strategies to mitigate these risks (Akbari et al 2015):…”

“…National agencies have also issued more specific recommendations for the safe use of gene drives (e.g., Germany, ZKBS 2016, USA; NASEM 2016; Australia; AAS 2017; France; HCB 2017; the Netherlands; RIVM 2018). However, as the technology is evolving rapidly, some of the international and national GMO regulatory frameworks need to be adapted to the specificities of gene drive organisms (Oye et al 2014;van der Vlugt et al 2018). In 2016, 160 civil society organizations called for a global moratorium on the development and release of the gene drive technology (ETC Group 2016).…”

A Cross-Sectional Survey of Biosafety Professionals Regarding Genetically Modified Insects

“…22 Insects containing these technologies present new containment challenges since active synthetic gene drive systems are designed to persist and increase in frequency in target populations as well as spread under certain conditions to other conspecific populations. [23][24][25][26] In some cases, such as so-called thresholdindependent gene drives, spread of the gene drive construct can be initiated with the release of a single gene drive-containing insect.…”