Transgene Biocontainment Strategies for Molecular Farming

Clark, Michael J.; Maselko, Maciej

doi:10.3389/fpls.2020.00210

Cited by 52 publications

(44 citation statements)

References 89 publications

(100 reference statements)

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“…The ability to rationally design reproductive barriers opens up diverse opportunities for pest management and biocontrol of invasive species as well as genetic containment of novel proprietary genetically modified organisms 24 . Underdominance-based gene drives are threshold-dependent and allow for localized population replacement 25 .…”

Section: Discussionmentioning

confidence: 99%

Engineering multiple species-like genetic incompatibilities in insects

Maselko

Feltman

Upadhyay

et al. 2020

Preprint

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24Speciation constrains the flow of genetic information between populations of sexually reproducing 25 organisms. Gaining control over mechanisms of speciation would enable new strategies to manage 26 wild populations of disease vectors, agricultural pests, and invasive species. Additionally, such 27 control would provide safe biocontainment of transgenes and gene drives. Natural speciation can 28 be driven by pre-zygotic barriers that prevent fertilization or by post-zygotic genetic 29 incompatibilities that render the hybrid progeny inviable or sterile. Here we demonstrate a general 30 approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila 31 melanogaster. Our system couples a dominant lethal transgene with a recessive resistance allele. 32 EGI strains that are homozygous for both elements are fertile and fecund when they mate with 33 similarly engineered strains, but incompatible with wild-type strains that lack resistant alleles. We 34show that EGI genotypes can be tuned to cause hybrid lethality at different developmental life-35 stages. Further, we demonstrate that multiple orthogonal EGI strains of D. melanogaster can be 36 engineered to be mutually incompatible with wild-type and with each other. Our approach to create 37 EGI organisms is simple, robust, and functional in multiple sexually reproducing organisms. 38 39 Main Text 40In genetics, underdominance occurs when a heterozygous genotype (Aa) is less fit than either 41 homozygous genotype (AA and aa). In 'extreme underdominance', the heterozygote is inviable while 42 each homozygote has equal fitness 1 . Extreme underdominance is an attractive and versatile tool for 43 population control. First, it could be leveraged to create threshold-dependent, spatially-contained 44 gene drives 2 capable of replacing local populations. Such gene drives may be more socially acceptable 45 than threshold-independent gene-drives to suppress populations since their spead can be more tightly 46 controlled. Alternatively, only males could be released for a genetic biocontrol approach that mimics 47 sterile insect technique. Several strategies for engineering underdominance have been described, 48including one-or two-locus toxin-antitoxin systems 3,4 , chromosomal translocations 5 , and RNAi-based 49 negative genetic interactions 6 . Despite its theoretical utility in population control, engineering 50 extreme underdominance has been difficult 1 . 51Extreme underdominance essentially constitutes a speciation event, as it prevents successful 52 reproduction and therefore genetic exchange between two populations. In nature, prezygotic and 53 postzygotic incompatibilities maintain species barriers. Prezygotic incompatibilities prevent 54 fertilization from taking place. These can include geographic separation or behavioral/anatomical 55 differences between individuals in two populations that prevent sperm and egg from meeting. 56Postzygotic incompatibilities occur when genetic or cellular differences between the maternal and 57 paterna...

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Section: Discussionmentioning

confidence: 99%

Engineering multiple species-like genetic incompatibilities in insects

Maselko

Feltman

Upadhyay

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The ability to rationally design reproductive barriers opens up diverse opportunities for pest management and biocontrol of invasive species as well as genetic containment of novel proprietary genetically modified organisms 23 . Underdominance-based gene drives are threshold-dependent and allow for localized population replacement 24 .…”

Section: Discussionmentioning

confidence: 99%

Engineering multiple species-like genetic incompatibilities in insects

et al. 2020

Self Cite

View full text Add to dashboard Cite

Speciation constrains the flow of genetic information between populations of sexually reproducing organisms. Gaining control over mechanisms of speciation would enable new strategies to manage wild populations of disease vectors, agricultural pests, and invasive species. Additionally, such control would provide safe biocontainment of transgenes and gene drives. Here, we demonstrate a general approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila melanogaster. EGI couples a dominant lethal transgene with a recessive resistance allele. Strains homozygous for both elements are fertile and fecund when they mate with similarly engineered strains, but incompatible with wild-type strains that lack resistant alleles. EGI genotypes can also be tuned to cause hybrid lethality at different developmental life-stages. Further, we demonstrate that multiple orthogonal EGI strains of D. melanogaster can be engineered to be mutually incompatible with wild-type and with each other. EGI is a simple and robust approach in multiple sexually reproducing organisms.

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“…Inefficient transgene biocontainment can incur great economic losses, as seen in the StarLink incident; moreover, pollen-mediated gene flow is a primary mode of unwanted biocontamination [54]. Determining the isolation distance between transgenic crops and sexually compatible crops is one of the various measures, including using pollen traps and buffer zones, to prevent pollen flow into neighboring fields [55].…”

Section: Discussionmentioning

confidence: 99%

Gene flow from transgenic soybean, developed to obtain recombinant proteins for use in the skin care industry, to non-transgenic soybean

et al. 2020

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Soybean has been recognized as a useful platform for heterologous protein production. This study compared the pollen characteristics of transgenic and non-transgenic soybean and investigated the rate of gene flow from transgenic soybean events, developed to obtain recombinant proteins (such as human epidermal growth factor, insulin-like growth factor 1, or thioredoxin) for use in the skin care industry, to non-transgenic soybean under field conditions, and determined the distance at which gene flow could occur. The lack of significant differences in pollen grain size, viability and pollen germination rates between transgenic and non-transgenic cultivars indicates that the overexpression of transgenes did not alter pollen characteristics in soybean. The highest rates of gene flow from the three transgenic soybean events to non-transgenic soybean ranged from 0.22 to 0.46% at the closest distance (0.5 m). Gene flow was observed up to 13.1 m from the transgenic plots. Our data fell within the ranges reported in the literature and indicate that an isolation distance greater than at least 13 m from transgenic soybean is required to prevent within-crop gene flow in soybean. As the potential markets for transgenic crops as a recombinant protein factory increase, gene flow from transgenic to non-transgenic conventional crops will become a key decision factor for policy makers during the approval process of transgenic crops. Our study may provide useful baseline data for the prevention of transgenic soybean seed contamination caused by transgene flow.

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Transgene Biocontainment Strategies for Molecular Farming

Cited by 52 publications

References 89 publications

Engineering multiple species-like genetic incompatibilities in insects

Engineering multiple species-like genetic incompatibilities in insects

Engineering multiple species-like genetic incompatibilities in insects

Gene flow from transgenic soybean, developed to obtain recombinant proteins for use in the skin care industry, to non-transgenic soybean

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