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Summary    Homing endonuclease genes ( HEG s) exist naturally in many single‐celled organisms and can show extremely strong genetic drive allowing them to spread through populations into which they are introduced. They are being investigated as tools to manipulate the populations of important vectors of human disease, in particular the mosquitoes that transmit malaria. Before  HEG s can be deployed, it is important to study their spatial spread in order to design efficient release strategies.  A spatially explicit model is developed to study the spread of a  HEG  through a landscape whose structure is defined by the distribution of mosquito breeding and feeding sites. The model is motivated by the biology of the major vectors of malaria in Africa. The conditions for spread, fixation and loss of two major types of  HEG  are explored in different landscapes.  In landscapes where mosquito resources are abundant, the conditions for spread are well approximated by a mean‐field model. Where a  HEG  imposes a genetic load, it can cause population extinction, though spatial models more often predict population suppression.  In certain types of landscapes where mosquito resources are rare, an introduced  HEG  may be prevented from moving between local mosquito populations and so a simple release strategy is unlikely to be effective, yet if the  HEG  succeeds in spreading population extinction is a feasible outcome. Increasing the number of release sites at the expense of releasing fewer mosquitoes per site reduces the probability that a  HEG  will fail.   Synthesis and applications . The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes ( HEG s) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of  HEG s through real landscapes where releases may take place, something that will be facilitated by the results of the present study.

Modelling the spatial spread of a homing endonuclease gene in a mosquito population