These recommendations represent the collective effort of working group members. They reflect a consensus opinion, acknowledging that individual participants had differing views on some issues. The issues addressed here are complex and cover a wide range of potential gene drive technologies. Therefore, these recommendations will need to be interpreted in a case-by-case manner depending on the nature of the investigational gene drive products and the environment where they are to be tested. The working group members agree that these recommendations provide important context and direction for further planning.
The term “threshold” refers to the proportion of modified mosquitoes with respect to the total mosquito population that will reliably initiate spread of the modification to high levels within the local mosquito population by mating. The goal of gene drive is to rapidly increase the proportion of vector mosquitoes carrying the beneficial modification. Low-threshold gene drives are defined here to include those that are predicted to spread from a rare introduction (zero threshold) or low initial release frequency.
Population suppression is sometimes called population reduction. Population replacement is sometimes termed population modification, population alteration, population transformation, or population conversion. The present article retains the terminology that was used in the WHO Guidance Framework.
The working group acknowledged that self-limiting or self-exhausting drive approaches might be useful in restricted locations, for other diseases or under other transmission conditions, and recognized the importance of modeling for making this determination.
It is possible that candidates may be imported in the form of a modified mosquito strain, most likely as eggs, to be interbred with local mosquitoes or as a DNA construct to be introduced into local mosquitoes by transfection.
This phase of testing is herein termed physical confinement, in keeping with the terminology of the WHO Guidance Framework,14 but is also widely known as containment. Recommendations are based on requirements recognized as Arthropod Containment Level (ACL), and the physical structure is standardly called a containment facility.
We thank the following for reviewing this report and providing valuable comments and suggestions: Jérémy Bouyer, Brinda Dass, Jason Delborne, Kevin Esvelt, Sarah Hartley, Calestous Juma, Daniel Masiga, Alan Pearson, Kent Redford, and Dominic White. We also thank Laren Friedman for creating the figures.
Beaty BJ, Prager DJ, James AA, Jacobs-Lorena M, Miller LH, Law JH, Collins FH, Kafatos FC, 2009. From Tucson to genomics and transgenics: the vector biology network and the emergence of modern vector biology. PLoS Negl Trop Dis 3: e343.
Adelman ZN, 2015. Genetic Control of Malaria and Dengue. Academic Press. New York, NY: Elsevier Science Publishing Co.
Macias VM, Ohm JR, Rasgon JL, 2017. Gene drive for mosquito control: where did it come from and where are we headed? Int J Environ Res Public Health 14: E1006.
Esvelt KM, Smidler AL, Catteruccia F, Church GM, 2014. Concerning RNA-guided gene drives for the alteration of wild populations. ELife 3: e03401.
Burt A, 2003. Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proc Biol Sci 270: 921–928.
Noble C, Adlam B, Church GM, Esvelt KM, Nowak MA, 2017. Current CRISPR gene drive systems are likely to be highly invasive in wild populations. bioRxiv, doi: 10.1101/219022.
Gantz VM, Jasinskiene N, Tatarenkova O, Fazekas A, Macias VM, Bier E, James AA, 2015. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proc Natl Acad Sci USA 112: E6736–E6743.
Hammond A et al. 2016. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol 34: 78–83.
Eckhoff PA, Wenger EA, Godfray HC, Burt A, 2017. Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics. Proc Natl Acad Sci USA 114: E255–E264.
Deredec A, Godfray HC, Burt A, 2011. Requirements for effective malaria control with homing endonuclease genes. Proc Natl Acad Sci USA 108: E874–E880.
World Health Organization, 2014. Guidance Framework for Testing of Genetically Modified Mosquitoes. Available at: http://apps.who.int/iris/bitstream/10665/127889/1/9789241507486_eng.pdf?ua=1. Accessed January 22, 2018.
Kaebnick GE, Heitman E, Collins JP, Delborne JA, Landis WG, Sawyer K, Taneyhill LA, Winickoff DE, 2016. Precaution and governance of emerging technologies. Science 354: 710–711.
VectorBase Bioinformatics Resource for Invertebrate Vectors of Human Pathogens. Anopheles gambiae s.l. Available at: https://www.vectorbase.org/taxonomy/anopheles-gambiae-sl. Accessed January 22, 2018.
Fontaine MC et al. 2015. Mosquito genomics. Extensive introgression in a malaria vector species complex revealed by phylogenomics. Science 347: 1258524.
Sinka ME et al. 2010. The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic precis. Parasit Vectors 3: 117.
Roche JP, 2015. Anopheles Mosquitoes as Vectors of Malaria in East Africa: Bed Nets and Beyond. Entomology Today: Entomological Society of America. Available at: https://entomologytoday.org/2015/04/24/anopheles-mosquitoes-as-vectors-of-malaria-in-east-africa-bed-nets-and-beyond/. Accessed January 22, 2018.
WHO, 2017. World Malaria Report 2017. World Health Organization. Available at: http://apps.who.int/iris/bitstream/10665/259492/1/9789241565523-eng.pdf?ua=1. Accessed January 22, 2018.
WHO, 2016. World Malaria Report 2016. World Health Organization. Available at: http://apps.who.int/iris/bitstream/handle/10665/252038/9789241511711-eng.pdf;jsessionid=8F359C7AF7CC0FEB0988D4690942A77F?sequence=1. Accessed May 4, 2018.
Nkumama IN, O’Meara WP, Osier FH, 2017. Changes in malaria epidemiology in Africa and new challenges for elimination. Trends Parasitol 33: 128–140.
Patouillard E, Griffin J, Bhatt S, Ghani A, Cibulskis R, 2017. Global investment targets for malaria control and elimination between 2016 and 2030. BMJ Glob Health 2: e000176.
World Health Organization, 2015. Global Technical Strategy for Malaria 2016–2030. Available at: http://apps.who.int/iris/bitstream/10665/176712/1/9789241564991_eng.pdf. Accessed January 22, 2018.
World Health Organization, 2017. Fifth Meeting of the Vector Control Advisory Group. Geneva, Switzerland, November 2–4, 2016. Available at: http://apps.who.int/iris/bitstream/10665/255824/1/WHO-HTM-NTD-VEM-2017.02-eng.pdf?ua=1. Accessed January 22, 2018.
Champer J, Buchman A, Akbari OS, 2016. Cheating evolution: engineering gene drives to manipulate the fate of wild populations. Nat Rev Genet 17: 146–159.
Noble C, Min M, Olejarz J, Buchthal J, Chavez A, Smidler AL, DeBenedictis EA, Church GM, Nowak MA, Esvelt KM, 2016. Daisy-chain gene drives for the alteration of local populations. bioRxiv, doi: 10.1101/057307.
Fischetti M, 2015. Africa Dwarfs China, Europe and the U.S. The Most Prevalent Flat Maps Make Africa Appear Much Smaller Than It Is. Scientific American: Springer Nature. Available at: https://www.scientificamerican.com/article/africa-dwarfs-china-europe-and-the-u-s/. Accessed January 22, 2018.
Derua YA, Alifrangis M, Magesa SM, Kisinza WN, Simonsen PE, 2015. Sibling species of the Anopheles funestus group, and their infection with malaria and lymphatic filarial parasites, in archived and newly collected specimens from northeastern Tanzania. Malar J 14: 104.
Djouaka RJ, Atoyebi SM, Tchigossou GM, Riveron JM, Irving H, Akoton R, Kusimo MO, Bakare AA, Wondji CS, 2016. Evidence of a multiple insecticide resistance in the malaria vector Anopheles funestus in south west Nigeria. Malar J 15: 565.
Beaghton A, Beaghton PJ, Burt A, 2017. Vector control with driving Y chromosomes: modelling the evolution of resistance. Malar