@article{Deredec2011,
abstract = {Malaria continues to impose a substantial burden on human health. We have previously proposed that biological approaches to control the mosquito vector of disease could be developed using homing endonuclease genes (HEGs), a class of selfish or parasitic gene that exists naturally in many microbes. Recent lab studies have demonstrated that HEGs can function in mosquitoes. We constructed and analyzed a model of mosquito population genetics and malaria epidemiology to determine how well HEGs need to function in order to have a significant effect on the burden of disease. Our model, combined with currently available data, indicates that populations of Anopheles gambiae could be eliminated by releasing 2-3 HEGs targeting female fertility genes, or a driving-Y chromosome that is transmitted to 75-96{\%} of progeny. Combinations of fertility-targeting HEGs and Y drive may also be effective. It is possible to eliminate the disease without eliminating the vector, but the parameter space producing this outcome appears to be small. HEGs causing a quantitative reduction in adult survival can be more effective than those targeting female fertility, but the selection coefficients that need to be imposed are still large, unless many HEGs are to be released. Simulations show that HEG-based strategies can be effective over socially relevant time frames. Important limiting assumptions of the models are that there is only a single vector species, and we model a homogeneous population, not a landscape. Nevertheless, we conclude that HEG-based approaches could have a transformational effect on malaria control efforts.},
author = {Deredec, Anne and Godfray, H Charles J and Burt, Austin},
doi = {10.1073/pnas.1110717108},
isbn = {0027-8424},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {43},
pages = {E874--80},
pmid = {21976487},
title = {{Requirements for effective malaria control with homing endonuclease genes.}},
url = {https://www.pnas.org/content/108/43/E874},
volume = {108},
year = {2011}
}
@article{Hancock2007,
abstract = {A series of models of malaria-mosquito-human interactions using the Lumped Age-Class technique of Gurney {\&} Nisbet are developed. The models explicitly include sub-adult mosquito dynamics and assume that population regulation occurs at the larval stage. A challenge for modelling mosquito dynamics in continuous time is that the insect has discrete life-history stages (egg, larva, pupa {\&} adult), the sub-adult stages of relatively fixed duration, which are subject to very different demographic rates. The Lumped Age-Class technique provides a natural way to treat this type of population structure. The resulting model, phrased as a system of delay-differential equations, is only slightly harder to analyse than traditional ordinary differential equations and much easier than the alternative partial differential equation approach. The Lumped Age-Class technique also allows the natural treatment of the relatively fixed time delay between the mosquito ingesting Plasmodium and it becoming infective. Three models are developed to illustrate the application of this approach: one including just the mosquito dynamics, the second including Plasmodium but no human dynamics, and the third including the interaction of the malaria pathogen and the human population (though only in a simple classical Ross-Macdonald manner). A range of epidemiological quantities used in studying malaria such as the vectorial capacity, the entomological inoculation rate and the basic reproductive number (R0) are derived, and examples given of the analysis and simulation of model dynamics. Assumptions and extensions are discussed. It is suggested that this modelling framework may be a natural and useful tool for exploring a variety of issues in malaria-vector epidemiology, especially in circumstances where a dynamic representation of mosquito recruitment is required.},
author = {Hancock, Penny A and Godfray, H Charles J},
doi = {10.1186/1475-2875-6-98},
isbn = {10.1186/1475-2875-6-98},
issn = {1475-2875},
journal = {Malaria journal},
keywords = {Animals,Culicidae,Culicidae: parasitology,Culicidae: physiology,Host-Parasite Interactions,Humans,Insect Vectors,Insect Vectors: parasitology,Larva,Larva: parasitology,Life Cycle Stages,Malaria,Malaria: epidemiology,Malaria: parasitology,Models, Biological,Mosquito Control,Plasmodium,Plasmodium: physiology,Population Dynamics},
pages = {98},
pmid = {17663757},
title = {{Application of the lumped age-class technique to studying the dynamics of malaria-mosquito-human interactions.}},
url = {https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-6-98},
volume = {6},
year = {2007}
}
@article{JohnMarshallAnnaBuchmanHectorMSanchezC.2017,
abstract = {Recent demonstrations of CRISPR-Cas9-based gene drive by Gantz et al. and Hammond et al. highlight the huge potential of this technology for the control of mosquito-borne diseases such as dengue, Zika and malaria through genetic modification of their vectors. Two promising strategies have been proposed - one in which the gene drive system is used to spread a disease-refractory gene into the mosquito population, and another in which the gene drive system is used to spread a fitness load or male gender bias, thus suppressing the mosquito population. While encouraging as a proof-of-concept, these constructs are highly error-prone and induce large fitness costs, leading to certain failure in the wild. Using a population modeling framework, we determine minimal properties that these systems must have in order to be successfully implemented. Required improvements address the following issues: a) disruption of the CRISPR-Cas9 target site through non-homologous end-joining (NHEJ); b) fitness costs induced by the transgene and/or gene drive system; and c) evolution of pathogen resistance to the disease-refractory gene. We use our modeling framework to explore potential solutions to these issues. For instance: a) the use of second or third-generation CRISPR-Cas9 systems to enable sustained population replacement or suppression; and b) the use of CRISPR-Cas9 systems that prevent the accumulation of NHEJ-generated mutant alleles by cleaving a target sequence in an essential gene while also containing a recorded copy of the essential gene. Finally, we project the dynamics of the constructs of Gantz et al. and Hammond et al. beyond the experimental data, and explore tailored improvements. High homing rates were observed for both constructs, with over 90{\%} transmission of the CRISPR-Cas9 system to offspring of heterozygous parents (c.f. 50{\%} expected for purely Mendelian inheritance); however, high rates of NHEJ were also recorded, and females heterozygous for the construct of Hammond et al. had their fertility reduced by 90{\%}. We recommend specific improvements for each system and thus suggest research priorities for the CRISPR-Cas9 gene drive field},
author = {Marshall, John and Buchman, Anna and C., Hector M Sanchez and Akbari, Omar S},
doi = {10.1038/s41598-017-02744-7},
file = {:Users/sanchez.hmsc/Library/Application Support/Mendeley Desktop/Downloaded/John Marshall, Anna Buchman, Hector M Sanchez C. - 2017 - Overcoming evolved resistance to population-suppressing homing-based gene driv.pdf:pdf;:Users/sanchez.hmsc/Library/Application Support/Mendeley Desktop/Downloaded/John Marshall, Anna Buchman, Hector M Sanchez C. - 2017 - Overcoming evolved resistance to population-suppressing homing-based gene d(2).pdf:pdf},
issn = {2045-2322},
journal = {Nature Scientific Reports},
keywords = {gene drive,homing,mathematical,multiplexing,population suppression,resistance alleles},
number = {June 2017},
pages = {1--46},
title = {{Overcoming evolved resistance to population-suppressing homing-based gene drives}},
url = {https://www.nature.com/articles/s41598-017-02744-7},
year = {2017}
}
