Transcript Slide 1

OXFORD INSECT TECHNOLOGIES
HEALTHY PEOPLE HEALTHY ENVIRONMENT
Genetic control of mosquitoes
Luke Alphey, Founder and Chief Scientific Officer
Visiting Professor in Zoology, University of Oxford
Oxitec Ltd
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Based in Oxford, UK,
30 employees
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Founded in 2002 to
commercialise new technology
from Oxford University
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Control of insects
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Agricultural pests
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Public Health (mosquitoes)
Injecting DNA into mosquito eggs
Introduction
Why?
 Pest insects cause $$bn damage and transmit major diseases
How?
 Engineered sterile males
 RIDL®: Release of Insects carrying a Dominant Lethal genetic system
 Genetics, molecular biology
When?
 Initial strains successfully tested in field
 Marker-only moth: USA 2006
 RIDL mosquitoes: Cayman Islands 2009, Malaysia 2010, Brazil 2011
Increased Risk of Vector Borne Disease
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Dengue - growing global pandemic
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Chikungunya - emerging threat
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Oxitec/Nimmo
Over 100 million cases annually
Severity increasing
No specific medication or vaccine
1.8 million cases in last 6 years
(WHO)
Reunion (2005) had 266,000 cases
and 254 deaths
Italy (2007) – 197 cases and I death
Dengue control
WHO
RIDL®
RIDL
A Genetic Solution
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Release engineered sterile
males to prevent mosquito
reproduction and so control
dengue
Based on Sterile Insect Technique
“birth control for mosquitoes”
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Sterile male mosquitoes
actively seek females
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How it works
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Find mosquitoes better than
human inspectors
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Rear millions of insects
Sterilise with irradiation
Release over wide area
Sterile males mate with wild
females: progeny don’t survive
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Pest population declines
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Species-specific
Used for over 50 years
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WHO
New World Screwworm Eradicated
RIDL: fail-safe / replacing radiation
RIDL insects are genetically sterile
 Repressible
 Release homozygous males
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Bi-sex lethal
Female-specific lethal
X
X
Introgression of genes through male line
RIDL®: molecular biology
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Controllable Gene Expression
Antidote
(Tc)
Female
death
death
tTA
promoter
effector
tetO
Female specificity
Thomas et al. 2000 Science 287: 2474-6
Fu et al. 2010 PNAS 107: 4550-4
Act4-tTA + tetO-DsRed
tTA
Act4 promoter
effector
(DsRed)
tetO + promoter
OX3545F
Flight muscles only
OX3604C RIDL mosquitoes
Males
Females
Flightless mosquitoes cannot survive in wild (or find hosts).
Unable to mate even in laboratory. Males have normal flight
ability, as have females given antidote as larvae.
fsRIDL phased trials – large lab cage trials
RIDL cage trials performed in Colorado State University (Megan Wise, Bill Black)
showing suppression of target population
RIDL: fail-safe / replacing radiation
RIDL insects are genetically sterile
 Repressible
 Release homozygous males

Bi-sex lethal
Female-specific lethal
X
X
Introgression of genes through male line
Development trials
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First open release Grand Cayman 2009
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mating of RIDL males to local females
excellent mating competitiveness
provided data for suppression trial 2010
10km
0
Each Area approx 16 Ha (40 acres)
No conventional control for Aedes aegypti
Release period May-Oct 2010 with pre- and post-release monitoring
500m
Cayman field trial 2010
Ovitrap Index (%)
OVITRAP INDEX treated (A) & non-treated (C)
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80
60
40
20
1-Apr
1-May
EE - Area C
1-Jun
1-Jul
EE - Area A
1-Aug
1-Sep
1-Oct
Poly. (EE - Area C)
Clear suppression from early August
Sustained release of RIDL OX513A males can suppress a field
population of Aedes aegypti mosquitoes
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0
Trial was complete success; all endpoints met
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0
Maximum degree of suppression limited by immigration
GM mosquitoes can perform successfully in the field
500m
Bringing new technology to the field
Antidote
(Tc)
death
effector
tTA
promoter
tetO
Technical
RIDL
Regulatory
Nature
Community
Regulatory Progress
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The USDA completed (2008) an Environmental
Impact Statement (EIS) on the use of autocidal
technology (RIDL) in fruit flies and PBW
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Record of Decision: this is the environmentally preferred alternative
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North American Plant Protection Organization
(NAPPO) standard signed late 2007
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MosqGuide: WHO/TDR develop guidance
for use of GM mosquitoes for disease control
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Oxitec transgenic insect approvals
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Multiple movement and contained trial approvals (Medfly, Mexfly, pink
bollworm, Aedes aegypti, Ae. albopictus)
Open field release approvals in the USA (PBW 2006,7,8)
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Released 15 million Oxitec pink bollworm from aircraft over 2500 acres (2008)
Community Engagement
Focus Group:
reactions to Oxitec approach
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breakthrough!
good news
kills larvae
good – something worth trying going forward
provides immediate solution / result in preventing
Dengue
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seen as a long term solution cf other methods which
are all seen as short term
•
some even welcome the research team to test the
technique in their community
From TNS Malaysia
Community engagement
• Malaysian Health Minister
Datuk Seri Liow Tiong Lai
“We see it as the most
efficient and fastest way in
eradicating Aedes
mosquitoes from our local
environment,” Liow said,
adding that Aedes is not a
species endemic [native] to
Malaysia. Monday 11th Oct
2010
Frequently Asked Questions
Will the genetic modification spread outside the release area?
The released mosquitoes and their progeny will die so this is a ‘self limiting’
approach, with no permanent change to the wild mosquito population. The large
fitness cost (and no component advantage) also prevents spread.
Do mosquitoes provide valuable ecosystem services (e.g. food chain, pollinators)?
Aedes aegypti originated in Africa and only achieved pan-tropical distribution in the
1930s. Therefore in most countries it is not a native species. There are no birds,
fish or other insects that feed exclusively on it and therefore reducing the number
of Aedes aegypti is most unlikely to have negative impacts on the environment.
If one mosquito suppressed, will a worse one replace (niche replacement)?
Aedes aegypti it occupies an unusual, human-associated niche normally empty in
its absence. Aedes albopictus, a potential alternative, is an inferior vector of
dengue. RIDL strains are also available for Aedes albopictus.
Can we release enough (feasibility, economics)?
Long history of success and data from SIT implies ‘yes’, as do modelling and data
so far.
Acknowledgements
Angi Harris
Bill Petrie
IMR, Malaysia
Lee Han Lim
OXFORD INSECT TECHNOLOGIES
HEALTHY PEOPLE HEALTHY ENVIRONMENT
Greg Simmons
Bob Staten (rtd)
Tom Miller (UCR)
PI: Tony James
PI: John Mumford
Thank you…