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Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2015
Eric S. Loker, Bruce V. Hofkin
Therefore, special mechanisms may need to be employed. For example, selfish genetic elements such as homing endonuclease genes could be used to drive the genes conferring resistance into natural populations. These selfish elements encode endonucleases that cleave a particular site in the genome and then effectively insert the genes encoding the endonuclease (and potentially engineered to contain anti -Plasmodium factors, too) into the cleaved site. In this way, they continually spread to other homologous sites that lack the endonuclease genes, inevitably becoming more common in the process. Some evidence suggests these drive mechanisms will work. If further work shows conclusively that we can successfully drive genetic elements conferring resistance into mosquito populations, then we also need to be sure that engineered Plasmodium-refractory mosquitoes are not also more refractory to all other mosquito pathogens as well; it would not be a good outcome to release super disease-resistant mosquitoes that then might become even more abundant than they already are. Also, this approach could quickly select for variants of Plasmodium that can overcome the engineered resistance genes. Although these may prove to be insurmountable problems, it can be argued we have nonetheless learned a great deal about mosquito biology, and this knowledge has paid off in other ways. For example, dengue virus vectors such as Aedes aegypti have been successfully infected with Wolbachia bacterial symbionts (see Chapters 2, 7, and 9 for more discussion of Wolbachia). These bacteria are close relatives of Wolbachia from Drosophila that are known to skew sex ratios, kill male flies, and favor fertilization only by males that are also infected. In the case of Wolbachia-bearingA. aegypti, they can spread upon release into natural populations and replace Wolbachia-freeA. aegypti. Furthermore, the bacterial infection is pathogenic enough to kill many dengue-infected mosquitoes before they can transmit the infection to another person. A similar goal—to reduce longevity of the infected vector below the developmental time required by the vectored parasite—could also be used to prevent Plasmodium infections from achieving sporozoite production (see Chapters 6 and 9). A similar approach could also be pursued for larval schis-tosomes developing in snails, which also take a long time to develop relative to the life spans of their snail hosts. That is, a way forward may be to exploit our knowledge of vector or intermediate host immunology just enough to prevent transmission from occurring.
Genes drive organisms and slippery slopes
Published in Pathogens and Global Health, 2022
David B. Resnik, Raul F. Medina, Fred Gould, George Church, Jennifer Kuzma
Selfish genetic elements are naturally occurring DNA sequences that bias inheritance in their favor so that they tend to increase in prevalence in a population, even if they negatively impact organismic fitness [1]. For more than sixty years, scientists have contemplated the possibility of using natural selfish genetic elements to control invasive or pest species and animal disease vectors, but technical challenges prevented these plans from coming to fruition [2–4]. The development of accurate and efficient gene editing tools, such as CRISPR (i.e. clustered regularly interspaced short palindromic repeats), has facilitated the construction of synthetic selfish genetic elements, commonly referred to as gene drives, and opened the door to engineering of wild populations [5–7]. 1Although CRISPR has received considerable attention in the scientific literature and the media, it is worth noting that other gene editing tools have been available since the 1970s and that more tools are likely to be developed in the future.[7].