Self-limiting Mosquitoes as a Tool for Vector Control Jennina Taylor-Wells, PhD 8 th February 2018 Page 1
Who is Oxitec? We provide insect control through novel technology that improves human health and food quality Through the reduction of insect populations Biological approach that is sustainable, economic and applicable to many insect species Page 2
Suppression of the Aedes aegypti mosquito SELF- LIMITING GENE Page 3
OX513A: A Self-limiting Friendly Aedes aegypti Inject genes into mosquito eggs Self-limiting Gene Fluorescent Marker Gene Self-limiting Gene Inherited - Offspring die prior to adulthood After releases stop, genes do not persist in the environment Repressed with an antidote (tetracycline) during insect production Fluorescent Marker Gene Fluorescent protein detected by microscope Identifies Oxitec insects vs. pest ones Estimation of pest population sizes and monitoring of suppression Adaptive releases based on tracking data Page 4
How our self-limiting technology works ttav Transcriptional machinery ttav works in a positive feedback loop to make more ttav ttav stops the mosquito from expressing essential genes Pest mosquito offspring die before they can reproduce In a production environment Tetracycline is added through the diet to block ttav action and this allows large scale production Page 5
Field trials show impressive results 96% 93% 99% 92% >90% suppression of Aedes aegypti in field trials and projects across Cayman Islands, Brazil, and Panama No reports of adverse effects on people or the environment 93% Cayman: Mosquito Research Control Unit Brazil: University of São Paulo and Moscamed Panama: The Gorgas Institute Page 6
Recent regulatory opinions for OX513A Regulatory milestones & EU publications for OX513A April 2014 August 2016 June 2017 June 2017 July 2017 October 2017 Brazil s CTNBio approval for commercial release FDA publishes FONSI & environmental assessment for trial in Florida Keys National Conservation Council of The Cayman Islands approved territory-wide operational use French High Council of Biotechnology recognizes the potential for use in French territories GMO office of the Dutch National Institute for Public Health & Environment - Positive evaluation of potential Regulatory jurisdiction moves from FDA to EPA - OX513A considered a biopesticide Page 7
Operational large-scale production facility: Piracicaba, Brazil Mass Production Real-time monitoring via fluorescent marker for adaptive releases Release is simple Page 8
Wild-type larva Self-limiting larva Innovation: Advancing our technology Self-Limiting Physical sorting males Lethal to both male and female offspring Selflimiting adult + Male-Selecting Genetic sorting to give males Lethal only to female offspring Page 9
Potential synergy with existing vector control tools Wild male Male-selecting, self-limiting Friendly Aedes aegypti may also protect or restore insecticide efficacy INSECTICIDE ONLY (IRS, ITN, sprays) Wild female OXITEC MALES ONLY Oxitec male Wild female OXITEC MALES + INSECTICIDE (IRS, ITN, sprays) Oxitec male Wild female S/r r/r S/S r/r S/S r/r S/r Resistance spreads = reduced efficacy of IRS, ITNs and sprayed insecticides r/r S/r S/r Male-selecting trait = > females, dilutes resistance genetics, offering resistance reversal S/r S/r Male-selecting trait + insecticide susceptibility = genetic sterility & slows spread of resistance Page 10
Self-limiting technology is transferable to other insects Public Health Target Mosquito Aedes aegypti Mosquito Aedes albopictus Vector of Dengue, Zika, & Chikungunya Dengue, Zika, & Chikungunya Agriculture Target Pink Bollworm Pectinophora gossypiella Fruit fly Drosophila suzukii Medfly Ceratitis capitata Olive fly Bactrocera oleae Diamondback Moth Plutella xylostella Crop Cotton Soft fruit Citrus/pome/ stone fruit Olive Brassica Page 11
Self-limiting technology demonstrated in human malaria vector An. stephensi Successful transformation of Anopheles species An. stephensi is a major malaria vector in the Indian subcontinent & distributed throughout the Middle East & China Page 12
Any Questions? jennina.taylor-wells@oxitec.com Page 13