Imperial College London

DrTonyNolan

Faculty of Natural SciencesDepartment of Life Sciences

Honorary Senior Lecturer
 
 
 
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Contact

 

t.nolan

 
 
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Assistant

 

Mrs Lucy Collyns +44 (0)20 7594 5395

 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Hammond:2018:10.1101/360339,
author = {Hammond, A and Kyrou, K and Gribble, M and Karlsson, X and Morianou, I and Galizi, R and Beaghton, A and Crisanti, A and Nolan, T},
doi = {10.1101/360339},
publisher = {Cold Spring Harbor Laboratory},
title = {Improved CRISPR-based suppression gene drives mitigate resistance and impose a large reproductive load on laboratory-contained mosquito populations},
url = {http://dx.doi.org/10.1101/360339},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - UNPB
AB - <jats:title>Abstract</jats:title><jats:p>CRISPR-based genes drives bias their own inheritance and can be used to modify entire populations of insect vectors of disease as a novel form of sustainable disease control. Gene drives designed to interfere with female fertility can suppress populations of the mosquito vector of malaria, however laboratory demonstrations showed strong unintended fitness costs and high levels of resistant mutations that limited the potential of the first generation of gene drives to spread. We describe three new gene drives designed to restrict spatio-temporal nuclease expression by using novel regulatory sequences. Two of the three new designs dramatically improve fitness and mitigate the creation and selection of resistance. We dissect the relative contributions of germline CRISPR activity versus embryonic CRISPR activity resulting from parental deposition, showing that the improved performance of the new designs is due to tighter germline restriction of the nuclease activity and significantly lower rates of end-joining repair in the embryo. Moreover, we demonstrate in laboratory-contained population experiments that these gene drives show remarkably improved invasion dynamics compared to the first generation drives, resulting in greater than 90% suppression of the reproductive output and a delay in the emergence of target site resistance, even at a loosely constrained target sequence. These results illustrate important considerations for gene drive design and will help expedite the development of gene drives designed to control malaria transmission in Africa.</jats:p>
AU - Hammond,A
AU - Kyrou,K
AU - Gribble,M
AU - Karlsson,X
AU - Morianou,I
AU - Galizi,R
AU - Beaghton,A
AU - Crisanti,A
AU - Nolan,T
DO - 10.1101/360339
PB - Cold Spring Harbor Laboratory
PY - 2018///
TI - Improved CRISPR-based suppression gene drives mitigate resistance and impose a large reproductive load on laboratory-contained mosquito populations
UR - http://dx.doi.org/10.1101/360339
ER -