Gene drives as a new quality in GMO releases—a comparative technology characterization

Abstract

Compared to previous releases of genetically modified organisms (GMOs) which were primarily plants, gene drives represent a paradigm shift in the handling of GMOs: Current regulation of the release of GMOs assumes that for specific periods of time a certain amount of GMOs will be released in a particular region. However, now a type of genetic technology arises whose innermost principle lies in exceeding these limits—the transformation or even eradication of wild populations. The invasive character of gene drives demands a thorough analysis of their functionalities, reliability and potential impact. But such investigations are hindered by the fact that an experimental field test would hardly be reversible. Therefore, an appropriate prospective assessment is of utmost importance for an estimation of the risk potential associated with the application of gene drives. This work is meant to support the inevitable characterization of gene drives by a comparative approach of prospective technology assessment with a focus on potential sources of risk. Therein, the hazard and exposure potential as well as uncertainties with regard to the performance of synthetic gene drives are addressed. Moreover, a quantitative analysis of their invasiveness should enable a differentiated evaluation of their power to transform wild populations.

CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues

“…While the introduction of small numbers of edited mosquitos or other pests is unlikely to cause major effects, gene drive is capable of copying mutations made on one chromosome by CRISPR to its partner chromosome, thus passing the edited genome on to future generations [ 177 ]. Although those dynamics could be instrumental in greatly limiting transmission rates of various infectious diseases, gene drives do entail considerable risks to the environment and ecosystems: they have in fact the potential to decimate entire species [ 178 , 179 ], disrupting food chains, or lead to the uncontrolled proliferation and spread of invasive species, without sufficient containment mechanisms [ 180 , 181 , 182 ]. It is therefore of utmost importance to identify the knowledge gaps that could thwart or complicate attempts to control CRISPR-modified species, as there may be unintended effects such as altering gene flow within a population [ 183 ].…”

Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post‐market environmental monitoring of genetically modified insects containing engineered gene drives

“…While research on engineered gene drives and their applications in insects is advancing at a fast pace, it is generally accepted that it will take several years for technological developments to move to practical applications for deliberate release into the environment. Drawing inspiration from systems that exist naturally, a variety of engineered gene drives have been progressed or theorised in recent years (reviewed by Sinkins and Gould, 2006;Champer et al, 2016;NASEM, 2016;Macias et al, 2017;Marshall and Akbari, 2018;R € udelsheim and Smets, 2018;CSS-ENSSER-VDW, 2019;Frieb et al, 2019;Raban et al, 2020). They encompass (see Table 2, below): Examples of engineered gene drives are briefly described below to illustrate the different approaches followed for GDMIs and their characteristics.…”

Using problem formulation for fit‐for‐purpose pre‐market environmental risk assessments of regulated stressors

“…As with any technology, however, true understanding of the potential risks to the environment must be informed by a case-specific risk assessment, not a generalised view of the technology (James et al, 2018;Frieß et al, 2019). One specific case example where the use of gene drive mechanisms has been proposed is to target vector mosquitoes in order to reduce or eliminate the spread of malaria (Gantz et al, 2015;Burt et al, 2018;Kyrou et al, 2018).…”

“…Within each category, different technical approaches [e.g. homing‐based drives using homing endonuclease genes; sex‐linked meiotic drives; Medea, the maternal effect dominant embryonic arrest system; underdominance or heterozygote inferiority drives; heritable microorganisms as illustrated by Wolbachia ; Frieß et al., )] with diverse characteristics are possible [e.g. conventional vs. integral gene drives (Nash et al., ); toxin‐antidote recessive embryo gene drives (Champer et al., ); allelic gene drives (Guichard et al., )].…”

“…The introduction of any new technology is accompanied by questions about associated risks. The potential to use a gene drive incorporated into a disease vectoring mosquito to reduce the incidence of malaria represents a departure from earlier methods of vector control (such as chemical sprays, use of physical barriers, and environment modification to eliminate breeding habitat), as well as from earlier releases of GMOs into the environment, which have primarily involved the use of GMOs for spatially limited uses, including crops for agriculture or sterile insect releases (Frieß et al., ). Because this application of genetic technology is novel, a great deal of attention is being given to considerations around ERA.…”