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Printable Handouts
Navigable Slide Index
- Introduction
- The malaria problem in numbers
- Anopheline mosquito serve as vectors
- Available tools to fight malaria
- Most effective malaria control measures
- Timeline of malaria eradication
- Ability to transmit malaria is genetically determined
- The challenge: spread a genetic modification into the population
- The allelic frequency of genetic modifications
- Genetic elements overcoming Mendelian inheritance (genetic drive)
- Molecular mechanisms of drive: Homing Endonuclease Genes (HEGs)
- Effect of genetic drive on inheritance
- Gene drive key points
- Gene drives may suppress entire populations of human malaria vectors
- Gene drive approaches for population suppression
- Sex chromosome drive
- Gene drive disruption of mosquito fertility genes
- Gene drive targeting recessive female fertility genes
- Identification of putative female fertility genes in Anopheles gambiae
- High rates of drive using CRISPR
- Sequencing of target site reveals several classes of mutations
- Monitoring target site sequence variation
- Understanding the molecular basis and genesis of resistance
- Molecular basis of resistance
- Gene drive induced resistance
- Approaches to overcome and limit resistance development
- Criteria for selecting the correct gene target
- The Anopheles gambiae 1000 genomes project database
- The gene doublesex meets several selection criteria
- The doublesex (dsx) of Anopheles gambiae
- Sex determination pathway in insects
- Validating dsx exon 5 for gene drive
- Exon 5 null phenotype in male and females
- Transgenic rate of gene drive targeting exon 5
- Population suppression experimental design
- Targeting ultraconserved regions that cause female sterility
- Functional Cas9 resistant mutants were not detected in cage trials
- Thank you
Topics Covered
- The malaria problem and the mosquito vector
- Spreading a genetic modification in a population
- The molecular mechanism of gene drive
- Gene drive for population control
- Efficiency of CRISPR-based gene drives
- Gene drive disruption of mosquito fertility genes
- Targeting the doublesex gene leading to population suppression without development of resistance
Links
Series:
- Gene-Drives and Active Genetics
- Periodic Reports: Advances in Clinical Interventions and Research Platforms
Categories:
Therapeutic Areas:
Talk Citation
Crisanti, A. (2021, February 28). CRISPR-based suppression drives for vector control [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved February 11, 2025, from https://doi.org/10.69645/USUP8228.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
A selection of talks on Infectious Diseases
Transcript
Please wait while the transcript is being prepared...
0:00
I'm Andrea Crisanti, I'm a professor of
molecular parasitology at Imperial College, London.
Today, I will talk about the work that we have carried
out in the lab during the last 10 years in
an effort to develop
a CRISPR-based suppression drive for vector control against malaria.
I'll take the opportunity to thank all the team in my lab,
the students, the technicians, the postdocs, and the research fellows.
Without their enthusiasm, dedication and knowledge,
the field of gene drive would be completely different today.
0:34
The next slide shows you why we are
interested in developing a vector control measure against malaria.
This disease is still one of the most important diseases
in the world, in terms of morbidity and mortality.
Half of the world's population is at risk from malaria, about 200 million people are infected every year, most of them in Africa.
About half a million people die as a consequence of malaria infection.
The people that die are either children or pregnant women,
these are the most vulnerable members of
the population in the poorest countries of the world.
1:10
Malaria is transmitted in Africa by
a few mosquito species belonging to the Anopheles genus,
which are Anopheles gambiae, Anopheles coluzzii,
Anopheles arabiensis and Anopheles funestus.
It's also important to remember that only the females transmit malaria.
Although there are 5,000 mosquito species in the world,
800 of which are in Africa,
only a few mosquito species transmit malaria.
1:36
The next slide shows what the available tools are to control malaria.
These are anti-malaria drugs, indoor residual spraying,
mosquito habitat removal, bed nets,
fumigation, and (with a question mark) vaccines.
Although researchers have been working on the development of a vaccine,
the available ones do not have the expected protection rates.