Genetic approaches to reducing vector competence of Aedes aegypti for chikungunya virus

Lead Research Organisation: The Pirbright Institute

Abstract

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Technical Summary

Dengue, chikungunya and other arboviral diseases impose significant morbidity and mortality. In few cases are licensed drugs or vaccines available. However, the dependence of these viruses on specific mosquito species, combined with advances in mosquito synthetic biology, potentially provides new approaches. We will engineer reduced-vector-competence traits in the major vector mosquito Aedes aegypti, focusing on chikungunya virus, though successful development would be
significant for a much wider range of viruses. We will pursue three approaches in parallel (i) to mitigate the risk that one of these ambitious approaches may not fully achieve its design goals; (ii) to provide multiple independent means to interfere with virus transmission, which in combination would greatly reduce the possibility of virus escape mutants. Two of these approaches aim to make mosquito cells more resistant to incoming viruses, (exploiting RNAi and super-infection exclusion mechanisms, respectively), the other aims to kill cells on infection so that they are unable to support virus transmission, using synthetic substrates for virus replicase that will be replicated and expressed following infection. Each of these approaches is inspired by natural anti-virus defence mechanisms and uses components and designs based on our strong collective track record in molecular virology and mosquito synthetic biology.

Publications

10 25 50
 
Description IUCN Technical Subgroup on Synthetic Biology and Biodiversity Conservation
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description Netherlands Commission on Genetic Modification (COGEM) Project "Gene drives, inventory of previous research and experience"
Geographic Reach Europe 
Policy Influence Type Gave evidence to a government review
 
Description RCUK Engagement workshop, Cosener's House, 20-21 April 2017
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description SACGM(CU) member 2014-present
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact The Scientific Advisory Committee on Genetic Engineering (Contained Use), SACGM(CU), provides technical and scientific advice to HSE and Ministers for the Department for Environment, Food and Rural Affairs, as well as their counterparts in Scotland, Wales and Northern Ireland. It has been in existence since 2004; I have been a member since 2014
URL https://webcommunities.hse.gov.uk/connect.ti/SACGM/grouphome
 
Description Engineering mosquitoes for reduced vector competence for chikungunya virus 
Organisation University of Malaya
Department Department of Medical Microbiology
PI Contribution Developed joint research programme, led successful application for funding, coordinate programme.
Collaborator Contribution Various specific strands of research, and group discussions about results, conclusions, research progress and future activities.
Impact reported under funding
Start Year 2016
 
Description Engineering mosquitoes for reduced vector competence for chikungunya virus 
Organisation University of Melbourne
Country Australia 
Sector Academic/University 
PI Contribution Developed joint research programme, led successful application for funding, coordinate programme.
Collaborator Contribution Various specific strands of research, and group discussions about results, conclusions, research progress and future activities.
Impact reported under funding
Start Year 2016
 
Description Engineering mosquitoes for reduced vector competence for chikungunya virus 
Organisation University of Tartu
Department Institute of Technology
PI Contribution Developed joint research programme, led successful application for funding, coordinate programme.
Collaborator Contribution Various specific strands of research, and group discussions about results, conclusions, research progress and future activities.
Impact reported under funding
Start Year 2016
 
Description Amy Lewis, The Scientist, 15/08/2017 re gene drive and Predator Free NZ 2050 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Provided information and quotes for article on potential use of gene drives as part of New Zealand effort to eradicate invasive predators
Year(s) Of Engagement Activity 2017
URL https://www.the-scientist.com/?articles.view/articleNo/50180/title/Driving-Down-Pests/
 
Description Biotech YES, Syngenta Jealott's Hill, 05 Oct 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Teams of postgraduate students from a number of universities and institutes attended talk as part of Biotech YES (Young Entrepreneurs' Scheme). Follow-up discussion influenced several aspects of their approach to entrepreneurship both within the competition and more generally
Year(s) Of Engagement Activity 2014,2015,2016,2017
 
Description CBD Open-ended online forum on synbio 06-10/2017 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact UN Convention on Biodiversity. Policy- discussion on synthetic biology: nominated participant in the Open Ended Online Forum on Synthetic biology as established in decision XII/24 of the Conference of the Parties to the Convention on Biological Diversity (COP) and extended in COP decision XIII/17 which ran from June to Oct 2017 (approx.)
Year(s) Of Engagement Activity 2017
URL http://bch.cbd.int/synbio/open-ended/discussion/
 
Description Caroline Seydel Genetic Literacy Project re GM mosquitoes/gene drive/Zika 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Provided background material and quotes for article on GM mosquitoes and control of Zika virus.
Year(s) Of Engagement Activity 2017
URL https://geneticliteracyproject.org/2018/01/29/waging-war-mosquito-split-gene-drive-hinder-spread-zik...
 
Description DARPA visit April 2017 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Supporters
Results and Impact Hosted visit by US funding agency programme manager to The Pirbright Institute
Year(s) Of Engagement Activity 2017
 
Description Ewen Callaway Nature 08/01/2018 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Provided expert background information for article in Nature regarding engineering species barriers, described by journalist as "very helpful" in followup email.
Year(s) Of Engagement Activity 2018
 
Description Invited seminar at UC Riverside 05/05/2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar at University of California, Riverside
Year(s) Of Engagement Activity 2017
 
Description Invited seminar at the University of Nottingham seminar series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact An invited seminar entitled: "Arbovirus encephalitis: from tissue culture, to mosquitoes to mice" was delivered. Discussions for potential collaborations followed.
Year(s) Of Engagement Activity 2017
 
Description Invited speaker at a workshop on arboviruses and their vectors in University of Malaya - Malaysia 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk entitled: " The role of small RNAs in arbovirus infections" was delivered. Multiple questions and requests for collaborations followed the presentation.
Year(s) Of Engagement Activity 2017
 
Description Malaysia workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Organised and participated in workshop on genetic control of mosquitoes, primarily focusing on refractory methods. Included a set of open lectures from international speakers at University of Malaysia and more focus workshop-style meetings. Several reported changes to research activities and also opinions, also follow-up meeting organized in Glasgow later in 2017
Year(s) Of Engagement Activity 2017
 
Description Nick Rufford, Sunday Time Mag, published 27/08/2017 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Provided information and quotes for Sunday TImes Magazine article on GM mosquitoes and Zika
Year(s) Of Engagement Activity 2017
URL https://www.thetimes.co.uk/article/how-genetically-engineered-mosquitoes-will-save-lives-kwc8nmwh5
 
Description Princess Anne opening Jenner 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Princess Anne, entourage, local politicians and dignitaries visited to open new research building. I was one of small number asked to present/demonstrate/describe our research work, which is on genetic modification of mosquitoes to provide new tools with which to help control mosquito-borne viral diseases.
Year(s) Of Engagement Activity 2017
 
Description Royal Society of Biology Biology week talk, Winchester, 10/10/2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk organized by Royal Society of Biology as part of Biology Week. This one in Winchester, audience was general public with strong representation of school-age. Questions and discussion during and after formal talk.
Year(s) Of Engagement Activity 2017