This is a database of peer-reviewed literature that focuses on Genetic Biocontrol research. The latest are shown here.
Malaria Vaccines: Progress to Date
Background
Malaria is a mosquito-borne disease caused by protozoan parasites of the genus Plasmodium. Despite significant declines in malaria-attributable morbidity and mortality over the last two decades, it remains a major public health burden in many countries. This underscores the critical need for improved strategies to prevent, treat and control malaria if we are to ultimately progress towards the eradication of this disease. Ideally, this will include the development and deployment of a highly effective malaria vaccine that is able to induce long-lasting protective immunity. There are many malaria vaccine candidates in development, with more than a dozen of these in clinical development. RTS,S/AS01 (also known as Mosquirix) is the most advanced malaria vaccine and was shown to have modest efficacy against clinical malaria in phase III trials in 5- to 17-month-old infants. Following pilot implementation trials, the World Health Organisation has recommended it for use in Africa in young children who are most at risk of infection with P. falciparum, the deadliest of the human malaria parasites.
Stanisic, D.I., Good, M.F. Malaria Vaccines: Progress to Date. BioDrugs (2023).
Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria
Background
Population suppression gene drive is currently being evaluated, including via environmental risk assessment (ERA), for malaria vector control. One such gene drive involves the dsxFCRISPRh transgene encoding (i) hCas9 endonuclease, (ii) T1 guide RNA (gRNA) targeting the doublesex locus, and (iii) DsRed fluorescent marker protein, in genetically-modified mosquitoes (GMMs). Problem formulation, the first stage of ERA, for environmental releases of dsxFCRISPRh previously identified nine potential harms to the environment or health that could occur, should expressed products of the transgene cause allergenicity or toxicity.
Qureshi, A., & Connolly, J. B. (2023). Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria. Malaria Journal, 22(1), 234.
A natural gene drive system confers reproductive isolation in rice
Background
- DUYAO-JIEYAO encodes a toxin-antidote system that confers hybrid male sterility
- DUYAO interacts with OsCOX11 to trigger mitochondrial malfunction and cytotoxicity
- JIEYAO detoxifies DUYAO by rerouting DUYAO to the autophagosome for degradation
- DUYAO-JIEYAO forms a natural gene drive system that may promote speciation in rice
Such a natural gene drive could be engineered to reduce female mosquito transmitted diseases in humans by generating homozygous sterile female mosquitos or male-only populations. Indeed, it will be exciting to see such a system fully exploited for biotechnology and biomedical purposes.
Wang, C., Wang, J., Lu, J., Xiong, Y., Zhao, Z., Yu, X., … & Wan, J. (2023). A natural gene drive system confers reproductive isolation in rice. Cell, 186(17), 3577-3592.
A confinable female-lethal population suppression system in the malaria vector, Anopheles gambiae
Background
Malaria is among the world’s deadliest diseases, predominantly affecting Sub-Saharan Africa and killing over half a million people annually. Controlling the principal vector, the mosquito Anopheles gambiae, as well as other anophelines, is among the most effective methods to control disease spread. Here, we develop a genetic population suppression system termed Ifegenia (inherited female elimination by genetically encoded nucleases to interrupt alleles) in this deadly vector. In this bicomponent CRISPR-based approach, we disrupt a female-essential gene, femaleless (fle), demonstrating complete genetic sexing via heritable daughter gynecide.
Smidler, A. L., Pai, J. J., Apte, R. A., Sánchez C, H. M., Corder, R. M., Jeffrey Gutiérrez, E., … & Akbari, O. S. (2023). A confinable female-lethal population suppression system in the malaria vector, Anopheles gambiae. Science Advances, 9(27), eade8903.
Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
Background
Novel genetic strategies for the malaria eradication agenda exploit Cas9/gRNA (guide RNA)-based autonomous gene-drive systems carrying antiparasite effector genes, and these effectively reduce prevalence and numbers of the human parasite, Plasmodium falciparum, in the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii. Results from laboratory assessments of population gene-drive dynamics, transgene genetic loads, and parasite suppression efficacy informed modeling of conceptual field releases that show that hypothetical strains based on the empirical data could have a meaningful epidemiological impact in reducing human incidence by 50 to 90%.
Carballar-Lejarazú, R., Dong, Y., Pham, T. B., Tushar, T., Corder, R. M., Mondal, A., … & James, A. A. (2023). Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii. Proceedings of the National Academy of Sciences, 120(29), e2221118120.
Wolbachia-based strategies for control of agricultural pests
Background
Wolbachia-based incompatible insect technique (IIT) and pathogen blocking technique (PBT) have been shown to be effective at protecting humans from mosquito-borne diseases in the past decades. Population suppression based on IIT and population replacement based on PBT have become major field application strategies that have continuously been improved by the translational research on Wolbachia-transinfected mosquitoes. Similarly, Wolbachia-based approaches have been proposed for the protection of plants from agricultural pests and their associated diseases.
Gong, J. T., Li, T. P., Wang, M. K., & Hong, X. Y. (2023). Wolbachia-based strategies for control of agricultural pests. Current Opinion in Insect Science, 101039.
The optimal strategy of incompatible insect technique (IIT) using Wolbachia and the application to malaria control
Background
For decades, techniques to control vector population with low environmental impact have been widely explored in both field and theoretical studies. The incompatible insect technique (IIT) using Wolbachia, based on cytoplasmic incompatibility, is a technique that Wolbachia-infected male mosquitoes are incapable of producing viable offspring after mating with wild-type female mosquitoes.
Matsufuji, T., & Seirin-Lee, S. (2023). The optimal strategy of incompatible insect technique (IIT) using Wolbachia and the application to malaria control. Journal of Theoretical Biology, 111519.
Gene Drives as Interventions into Nature: the Coproduction of Ontology and Morality in the Gene Drive Debate
Background
Gene drives are potentially ontologically and morally disruptive technologies. The potential to shape evolutionary processes and to eradicate (e.g. malaria-transmitting or invasive) populations raises ontological questions about evolution, nature, and wilderness. The transformative promises and perils of gene drives also raise pressing ethical and political concerns.
Boersma, K., Bovenkerk, B., & Ludwig, D. (2023). Gene Drives as Interventions into Nature: the Coproduction of Ontology and Morality in the Gene Drive Debate. NanoEthics, 17(1), 4.
The boundary problem: Defining and delineating the community in field trials with gene drive organisms
Background
Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch.
de Graeff, N., Pirson, I., van der Graaf, R., Bredenoord, A. L., & Jongsma, K. R. (2023). The boundary problem: Defining and delineating the community in field trials with gene drive organisms. Bioethics.
The Promise and Challenge of Genetic Biocontrol Approaches for Malaria Elimination
Background
Malaria remains an ongoing public health challenge, with over 600,000 deaths in 2021, of which approximately 96% occurred in Africa. Despite concerted efforts, the goal of global malaria elimination has stalled in recent years. This has resulted in widespread calls for new control methods. Genetic biocontrol approaches, including those focused on gene-drive-modified mosquitoes (GDMMs), aim to prevent malaria transmission by either reducing the population size of malaria-transmitting mosquitoes or making the mosquitoes less competent to transmit the malaria parasite.
James, S., & Santos, M. (2023). The Promise and Challenge of Genetic Biocontrol Approaches for Malaria Elimination. Tropical Medicine and Infectious Disease, 8(4), 201.