Imperial College London
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ProfessorAustinBurt

Faculty of Natural Sciences, Department of Life Sciences (Silwood Park)

Professor of Evolutionary Genetics
 
 
 
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Contact

 

+44 (0)20 7594 2266a.burt

 
 
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Location

 

Silwood ParkSilwood Park

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Summary

 

Publications

Citation

BibTex format

@article{North:2020:10.1186/s12915-020-00834-z,
author = {North, AR and Burt, A and Godfray, HCJ},
doi = {10.1186/s12915-020-00834-z},
journal = {BMC Biology},
title = {Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility},
url = {http://dx.doi.org/10.1186/s12915-020-00834-z},
volume = {18},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Gene drives based on CRISPR-Cas9 technology are increasingly being considered as tools for reducing the capacity of mosquito populations to transmit malaria, and one of the most promising options is driving endonuclease genes that reduce the fertility of female mosquitoes. In particular, there is much interest in constructs that target the conserved mosquito doublesex (dsx) gene such that the emergence of functional drive-resistant alleles is unlikely. Proof of principle that these constructs can lead to substantial population suppression has been obtained in population cages, and they are being evaluated for use in sub-Saharan Africa. Here, we use simulation modelling to understand the factors affecting the spread of this type of gene drive over a one million-square kilometre area of West Africa containing substantial environmental and social heterogeneity. RESULTS: We found that a driving endonuclease gene targeting female fertility could lead to substantial reductions in malaria vector populations on a regional scale. The exact level of suppression is influenced by additional fitness costs of the transgene such as the somatic expression of Cas9, and its deposition in sperm or eggs leading to damage to the zygote. In the absence of these costs, or of emergent drive-resistant alleles that restore female fertility, population suppression across the study area is predicted to stabilise at ~ 95% 4 years after releases commence. Small additional fitness costs do not greatly affect levels of suppression, though if the fertility of females whose offspring transmit the construct drops by more than ~ 40%, then population suppression is much less efficient. We show the suppression potential of a drive allele with high fitness costs can be enhanced by engineering it also to express male bias in the progeny of transgenic males. Irrespective of the strength of the drive allele, the spatial model predicts somewhat less suppression than equivalent
AU  - North,AR
AU  - Burt,A
AU  - Godfray,HCJ
DO  - 10.1186/s12915-020-00834-z
PY  - 2020///
SN  - 1741-7007
TI  - Modelling the suppression of a malaria vector using a CRISPR-Cas9 gene drive to reduce female fertility
T2  - BMC Biology
UR  - http://dx.doi.org/10.1186/s12915-020-00834-z
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32782000
UR  - http://hdl.handle.net/10044/1/81897
VL  - 18
ER  -
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