Improve engineering of select insects for safe, effective environmental deployment.

Engineering Biology

Environmental Biotechnology Challenge:

Controlled deployment of engineered organisms to improve ecosystem biodiversity, robustness, and the well-being of inhabitants.

Improve engineering of select insects for safe, effective environmental deployment.

Engineering Biology Objectives & Technical Achievements

Design and produce insects with safe and effective gene drives to combat the spread of vector-borne infectious diseases.¹

Engineering DNA	Biomolecular Engineering	Host Engineering	Data Science
Gene engineering capabilities for producing targeted sterility in insects/arachnids regardless of species. Gene editing capabilities to enhance vector resistance to parasites.	Improve ability to target vector reproductive capabilities without off-target effects and ride-along mutations.	Ability to introduce genetically-encoded “kill switches” such as auxotrophies dependent on localized, environmentally-available compounds. Ability to enhance host (vector) antibody production against specific pathogen antigens.	Better predictive long-term environmental and disease models incorporating climate change data with sterile vector release programs. Increase automation capabilities for gene editing and rearing large numbers of sterile vectors of different species.

Engineering DNA

Biomolecular Engineering

Host Engineering

Data Science

Gene engineering capabilities for producing targeted sterility in insects/arachnids regardless of species.

Gene editing capabilities to enhance vector resistance to parasites.

Improve ability to target vector reproductive capabilities without off-target effects and ride-along mutations.

Ability to introduce genetically-encoded “kill switches” such as auxotrophies dependent on localized, environmentally-available compounds.

Ability to enhance host (vector) antibody production against specific pathogen antigens.

Better predictive long-term environmental and disease models incorporating climate change data with sterile vector release programs.

Increase automation capabilities for gene editing and rearing large numbers of sterile vectors of different species.

Characterize and engineer natural microorganisms to control insect populations.²

Engineering DNA	Biomolecular Engineering	Host Engineering	Data Science
Engineer new genomic programs, such as combinations of synthetic auxotrophies, that increase the safety and reduce the risk of deploying engineered microbes in the field. Knockouts to validate candidate gene(s) in Wolbachia (a common parasitic microbe) to confirm genotype-to-phenotype models, to use Wolbachia as a biological tool for controlling insect populations.	Identify key biomolecular interactions involved in host-microbe interactions to prepare for future engineering.	Validate function of candidate native microbial organisms. Genome engineering capabilities for implementing large numbers of targeted modifications in specific hosts that may have limited tools for transformation, modification and programmable gene expression.	Genotype-to-phenotype tools for what makes Wolbachia function for controlling vector reproduction/fitness and other physiological functions. Genotype-to-phenotype tools for identifying candidate organisms from natural populations. Automation in rearing/sexing of infected organisms to fit use requirements.

Engineering DNA

Biomolecular Engineering

Host Engineering

Data Science

Engineer new genomic programs, such as combinations of synthetic auxotrophies, that increase the safety and reduce the risk of deploying engineered microbes in the field.

Knockouts to validate candidate gene(s) in Wolbachia (a common parasitic microbe) to confirm genotype-to-phenotype models, to use Wolbachia as a biological tool for controlling insect populations.

Identify key biomolecular interactions involved in host-microbe interactions to prepare for future engineering.

Validate function of candidate native microbial organisms.

Genome engineering capabilities for implementing large numbers of targeted modifications in specific hosts that may have limited tools for transformation, modification and programmable gene expression.

Genotype-to-phenotype tools for what makes Wolbachia function for controlling vector reproduction/fitness and other physiological functions.

Genotype-to-phenotype tools for identifying candidate organisms from natural populations.

Automation in rearing/sexing of infected organisms to fit use requirements.

Increase diversification and resilience of capable insect pollinators.

Engineering DNA	Biomolecular Engineering	Host Engineering	Data Science
Knockout or gain-of-function systems to validate semiochemical attractant/repellent pathways in candidate animals. Identification of genes involved in susceptibility to various pollinator pathogens and/or toxins (e.g., honey bee susceptibility to Varroa mites).	Ability to affect multiple genes, with minimal off-target physiological effects, to achieve increased resistance to pollinator pathogens and toxins.	Demonstrate functional circuits conferring host-insect attraction in engineered insects. Validate function, viability, and behavior of candidate native organisms.	Accurate prediction of plant-insect pairs and potential ecological off-target pairs. Increased automation capabilities for gene editing and rearing large numbers of disease-resistant pollinators.

Engineering DNA

Biomolecular Engineering

Host Engineering

Data Science

Knockout or gain-of-function systems to validate semiochemical attractant/repellent pathways in candidate animals.

Identification of genes involved in susceptibility to various pollinator pathogens and/or toxins (e.g., honey bee susceptibility to Varroa mites).

Ability to affect multiple genes, with minimal off-target physiological effects, to achieve increased resistance to pollinator pathogens and toxins.

Demonstrate functional circuits conferring host-insect attraction in engineered insects.

Validate function, viability, and behavior of candidate native organisms.

Accurate prediction of plant-insect pairs and potential ecological off-target pairs.

Increased automation capabilities for gene editing and rearing large numbers of disease-resistant pollinators.

Footnotes

Gantz, V. M., & Bier, E. (2015). Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations. Science, 348(6233), 442–444. View publication.; Kyrou, K., Hammond, A. M., Galizi, R., Kranjc, N., Burt, A., Beaghton, A. K., … Crisanti, A. (2018). A CRISPR-Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nature Biotechnology, 36(11), 1062–1066. View publication.; Bier, E., Harrison, M. M., O’Connor-Giles, K. M., & Wildonger, J. (2018). Advances in Engineering the Fly Genome with the CRISPR-Cas System. Genetics, 208(1), 1–18. View publication.; Gantz, V. M., Jasinskiene, N., Tatarenkova, O., Fazekas, A., Macias, V. M., Bier, E., & James, A. A. (2015). Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proceedings of the National Academy of Sciences of the United States of America, 112(49), E6736-43. View publication.
Gilbert, J. A., & Melton, L. (2018). Verily project releases millions of factory-reared mosquitoes. Nature Biotechnology, 36(9), 781–782. View publication.; National Research Council (US) Committee on Scientific Evaluation of the Introduction of Genetically Modified Microorganisms and Plants into the Environment. (1989). Field testing genetically modified organisms: framework for decisions.Washington (DC): National Academies Press (US). View publication.