Transgenic mosquitoes: A future vector control strategy?

Parasitology Today, vol. 6, no. 2, 1990

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Transgenic Mosquitoes: A Future Vector Control Strategy? J. Crampton, A. Morris, G. Lycett, A. Warren and P. Eggleston Transgenic mosquitoes r,~y provide a new way of dealing with the old problem of diseases transmitted by insects. Although many technical, and perhaps ethical, problems associated with the wild-release of transgenic insects have yet to be overcome, Julian Crampton and colleagues explore the potential of this technology in the continuing battle to control insect-borne disease. The genetic control of insect populations is not new. Until the advent of recombinant DNA technology the most promising autocidal methods were the mass release of sterile mal[esx,2 and the generation of cytogenetically induced sterility through translocations or compound clhromosomes3. Initial experiments with the mass release of sterile Aedes aegypti males were unsuccessful4, probably because of the use of crude and debilitating chemoand radio-sterilants that impaired reproductive competitiveness in the released males. Less harsh procedures have since enjoyed considerable success in other insect species 5. The introduction and propagation of specific genes and marked chromosomes has been field-tested in collaboration with the WHO and the Indian Council for Medical Research. The release of adults into two natural populations of Ae. aegypti for approximately three weeks resulted in the incorporation of a dominant gene (Silver mesonotum) and a male-linked translocation, both of which persisted for several generations after release6. The genetic marker was even found in the following breeding season. Fun:hermore, there was also evidence that the translocation caused some degree of sterility. Compared with classical techniques, two particular advantages of genetic engineering are evident. One is the potential to exploit genes across species barriers and the other is the ability to introduce defined DNA sequences without the genome disruption that accompanies a conventional cross. But this presupposes that :mosquitoes become as genetically well-defined as Drosophila melanogaster, and it is vital that target genes are identified that are suitable for manipulation or disruption. A means of introducing manipulated DNA into mosquitoes is needed, together with an effic:ient DNA vector system that Julian Crampton, Gareth Lycett, Ann Warren and Paul Eggleston are at the Wolfson Unit of Molecular Genetics, Department of Medical Entomology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. Alison Morris is at the Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92717, USA. I~) 1990, Elsevier Science Publishers Ltd, (LIK) 016947071901502.00

will allow stable integration of the introduced DNA into the genome. This may not only have to be expressed, but should also provide a means of selecting transformed individuals. The stable transformation of the DNA of an organism can be achieved in a number of ways. (1) Random integration, where the introduced DNA integrates at random sites in chromosomal DNA, usually as multiple copies of tandem repeats. (2) Homologous recombination, where the transfected gene replaces a specific locus with which it has homology. (3) Transposition, where transposable genetic elements (transposons) allow a single unit of DNA to integrate into specific loci. (4) Episomal .transformation is suitable for those cases, for example m yeast, where transfected DNA is stable in an extrachromosomal form but only if it can replicate autonomously from one generation to the next. Transposition and homologous recombination offer various degrees of control of the integration site and are potentially of most use to inactivate or replace existing gene functions. Despite the availability of other gene transfer methods, vector transformation systems using transposable elements offer several potential advantages. For instance, exogenous DNA can be inserted into the recipient genome in a disseminated and stable manner, thus overcoming the problems, such as DNA rearrangement and instability, that limit the usefulness of plasmid vectors 7,s. Moreover, if plasmid vector sequences are linked to the gene under

Fig. I. An Aedes aegypti mosquito shortly after a blood meal.

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Fig. 2. Early Aedes aegypti embryos (