scholarly journals De-extinction and Gene Drives: The Engineering of Anthropocene Organisms

2021 ◽  
pp. 495-511
Author(s):  
Christopher J. Preston
Keyword(s):  
Genome Editing ◽  
Potential Problem ◽  
Human Agency ◽  
Gene Synthesis ◽  
Wild Populations ◽  
Relational Thinking ◽  
Speculative Ethics ◽  
Asking Questions ◽  
Gene Drives

AbstractAdvances in gene reading, gene synthesis, and genome editing are making possible a number of radical new practices for transforming animal futures in the Anthropocene. De-extinction may make it possible to bring back lost species. Gene drives may enable the sending of desirable traits through wild populations of organisms. The hype accompanying these promises can make each of them look ethically irresistible. This chapter investigates the ‘speculative ethics’ that has arisen around these technologies, asking questions about both their viability and the approach to animals they contain. Reductive and non-relational thinking is identified as one potential problem with the thinking behind these techniques. The neglect of non-human agency is identified as another. After indicating some of the problems these two ways of conceptualizing an animal and its genome can create, a brief suggestion is made about how to better conceptualize animal futures in the Anthropocene.

scholarly journals Cheating evolution: engineering gene drives to manipulate the fate of wild populations

2016 ◽  
Vol 17 (3) ◽  
pp. 146-159 ◽  
Author(s):  
Jackson Champer ◽  
Anna Buchman ◽  
Omar S. Akbari
Keyword(s):  
Wild Populations ◽  
Gene Drives

Machine Learning of Synthetic Biological Sequences for Designer Attribution

2019 ◽  
Author(s):  
Craig Howser ◽  
Claire Marie Filone ◽  
Jessica S Dymond ◽  
Brant Chee ◽  
Joseph Downs ◽  
...  
Keyword(s):  
Machine Learning ◽  
Genome Editing ◽  
Dna Sequence ◽  
Learning Model ◽  
Gene Synthesis ◽  
Biological Sequences ◽  
Genetic Sequence ◽  
Design And Optimization ◽  
Machine Learning Model ◽  
Design Software

Advances in genome editing and gene synthesis technologies have increased the ease with which biological agents can be engineered. Existing methods to identify the engineering source are insufficient for attribution. We hypothesized that strategies used for DNA design and optimization could act as identifiable fingerprints of design software or particular vendors, making engineered agents more attributable to their source. To test this hypothesis, sequences optimized using various gene synthesis vendors were characterized using a machine learning model. By capturing optimization signatures unique to each vendor, the trained model showed an ability to identify a sequences origin with an accuracy up to 92%, indicating it is possible to distinguish the algorithm utilized to optimize a genetic sequence based on the DNA sequence output alone.

scholarly journals Concerning RNA-guided gene drives for the alteration of wild populations

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Kevin M Esvelt ◽  
Andrea L Smidler ◽  
Flaminia Catteruccia ◽  
George M Church
Keyword(s):  
Invasive Species ◽  
Herbicide Resistance ◽  
Wild Populations ◽  
Genomic Changes ◽  
Ecological Problems ◽  
Political Borders ◽  
And Control ◽  
Gene Drives ◽  
Careful Assessment ◽  
General Method

Gene drives may be capable of addressing ecological problems by altering entire populations of wild organisms, but their use has remained largely theoretical due to technical constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR nuclease Cas9 to serve as a general method for spreading altered traits through wild populations over many generations. We detail likely capabilities, discuss limitations, and provide novel precautionary strategies to control the spread of gene drives and reverse genomic changes. The ability to edit populations of sexual species would offer substantial benefits to humanity and the environment. For example, RNA-guided gene drives could potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species. However, the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application. We call for thoughtful, inclusive, and well-informed public discussions to explore the responsible use of this currently theoretical technology.

scholarly journals Modulating CRISPR gene drive activity through nucleocytoplasmic localization of Cas9 in S. cerevisiae

2018 ◽  
Author(s):  
Megan E. Goeckel ◽  
Erianna M. Basgall ◽  
Isabel C. Lewis ◽  
Samantha C. Goetting ◽  
Yao Yan ◽  
...  
Keyword(s):  
Nuclease Activity ◽  
Gene Drive ◽  
Wild Populations ◽  
Vector Borne Diseases ◽  
Vector Borne ◽  
Mendelian Laws ◽  
Artificial Gene ◽  
Nuclear Localization Sequences ◽  
Gene Drives

ABSTRACTThe bacterial CRISPR/Cas genome editing system has provided a major breakthrough in molecular biology. One use of this technology is within a nuclease-based gene drive. This type of system can install a genetic element within a population at unnatural rates. Combatting of vector-borne diseases carried by metazoans could benefit from a delivery system that bypasses traditional Mendelian laws of segregation. Recently, laboratory studies in fungi, insects, and even mice, have demonstrated successful propagation of CRISPR gene drives and the potential utility of this type of mechanism. However, current gene drives still face challenges including evolved resistance, containment, and the consequences of application in wild populations. In this study, we use an artificial gene drive system in budding yeast to explore mechanisms to modulate nuclease activity of Cas9 through its nucleocytoplasmic localization. We examine non-native nuclear localization sequences on Cas9 fusion proteins in vivo and demonstrate that appended signals can titrate gene drive activity and serve as a potential molecular safeguard.

scholarly journals Engineering multiple species-like genetic incompatibilities in insects

2020 ◽  
Author(s):  
Maciej Maselko ◽  
Nathan Feltman ◽  
Ambuj Upadhyay ◽  
Amanda Hayward ◽  
Siba Das ◽  
...  
Keyword(s):  
Life Stages ◽  
Agricultural Pests ◽  
Wild Type ◽  
Recessive Resistance ◽  
Wild Populations ◽  
Hybrid Lethality ◽  
Multiple Species ◽  
Type Strains ◽  
Gene Drives ◽  
New Strategies

AbstractSpeciation 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. Natural speciation can be driven by pre-zygotic barriers that prevent fertilization or by post-zygotic genetic incompatibilities that render the hybrid progeny inviable or sterile. Here we demonstrate a general approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila melanogaster. Our system couples a dominant lethal transgene with a recessive resistance allele. EGI strains that are 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. We show that EGI genotypes can 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. Our approach to create EGI organisms is simple, robust, and functional in multiple sexually reproducing organisms.

scholarly journals Evolutionary dynamics of CRISPR gene drives

2016 ◽  
Author(s):  
Charleston Noble ◽  
Jason Olejarz ◽  
Kevin M. Esvelt ◽  
George M. Church ◽  
Martin A. Nowak
Keyword(s):  
Evolutionary Dynamics ◽  
Evolutionary Stability ◽  
Clear Understanding ◽  
Gene Drive ◽  
Host Organism ◽  
Wild Populations ◽  
Selfish Genetic Elements ◽  
Real World Applications ◽  
Drive Systems ◽  
Gene Drives

AbstractThe alteration of wild populations has been discussed as a solution to a number of humanity’s most pressing ecological and public health concerns. Enabled by the recent revolution in genome editing, CRISPR gene drives, selfish genetic elements which can spread through populations even if they confer no advantage to their host organism, are rapidly emerging as the most promising approach. But before real-world applications are considered, it is imperative to develop a clear understanding of the outcomes of drive release in nature. Toward this aim, we mathematically study the evolutionary dynamics of CRISPR gene drives. We demonstrate that the emergence of drive-resistant alleles presents a major challenge to previously reported constructs, and we show that an alternative design which selects against resistant alleles greatly improves evolutionary stability. We discuss all results in the context of CRISPR technology and provide insights which inform the engineering of practical gene drive systems.

scholarly journals Switchable genome editing via genetic code expansion

2018 ◽  
Author(s):  
Toru Suzuki ◽  
Maki Asami ◽  
Sanjay G. Patel ◽  
Louis Y. P. Luk ◽  
Yu-Hsuan Tsai ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Genetic Code ◽  
Genome Editing ◽  
Active Form ◽  
Mammalian Genome ◽  
Gene Drive ◽  
Genetic Code Expansion ◽  
Or Gene ◽  
Gene Drives

AbstractMultiple applications of genome editing by CRISPR-Cas9 necessitate stringent regulation and Cas9 variants have accordingly been generated whose activity responds to small ligands, temperature or light. However, these approaches are often impracticable, for example in clinical therapeutic genome editing in situ or gene drives in which environmentally-compatible control is paramount. With this in mind, we have developed heritable Cas9-mediated mammalian genome editing that is acutely controlled by the cheap lysine derivative, Lys(Boc) (BOC). Genetic code expansion permitted non-physiological BOC incorporation such that Cas9 (Cas9BOC) was expressed in a full-length, active form in cultured somatic cells only after BOC exposure. Stringently BOC-dependent, heritable editing of transgenic and native genomic loci occurred when Cas9BOC was expressed at the onset of mouse embryonic development from cRNA or Cas9BOC transgenic females. The tightly controlled Cas9 editing system reported here promises to have broad applications and is a first step towards purposed, spatiotemporal gene drive regulation over large geographical ranges.

scholarly journals Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs

2017 ◽  
Vol 49 (1) ◽  
Author(s):  
Serap Gonen ◽  
Janez Jenko ◽  
Gregor Gorjanc ◽  
Alan J. Mileham ◽  
C. Bruce A. Whitelaw ◽  
...  
Keyword(s):  
Genome Editing ◽  
Genetic Gain ◽  
Breeding Programs ◽  
Livestock Breeding ◽  
Gene Drives

Genome Editing 2020: Ethics and Human Rights in Germline Editing in Humans and Gene Drives in Mosquitoes

2020 ◽  
Vol 46 (2-3) ◽  
pp. 143-165
Author(s):  
George J. Annas
Keyword(s):  
Human Rights ◽  
Genome Editing ◽  
Genomic Research ◽  
Ethical Standards ◽  
Space Travel ◽  
Dual Use ◽  
Genomic Engineering ◽  
The Past ◽  
Moon Landing ◽  
Gene Drives

The moon landing, now more than a half century in the past, has turned out to be the culmination of human space travel, rather than its beginning. Genetic engineering, especially applications of CRISPR, now presents the most publicly-discussed engineering challenges—and not just technical, but ethical as well. In this article, I will use the two most controversial genomic engineering applications to help identify the ethics and human rights implications of these research projects. Each of these techniques directly modifies the mechanisms of evolution, threatens to alter our views of ourselves as humans and our planet as our home, and presents novel informed consent and dual use challenges: human genome editing and gene drives in insects.I begin with a discussion of so far disastrously unsuccessful attempts to regulate germline editing in humans, including a summary of the first application of germline genome editing in humans and its aftermath. I then turn to a discussion of setting ethical standards for a genomic technology that has not yet been deployed in nature—gene drives. Finally, I end by suggesting that human rights can and should be directly applicable to defining the ethics of genomic research.

scholarly journals RNA-guided gene drives can efficiently and reversibly bias inheritance in wild yeast

2015 ◽  
Author(s):  
James E DiCarlo ◽  
Alejandro Chavez ◽  
Sven L Dietz ◽  
Kevin M Esvelt ◽  
George M Church
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Drive ◽  
Wild Type ◽  
Wild Populations ◽  
Yeast Saccharomyces Cerevisiae ◽  
Wild Yeast ◽  
Successive Generations ◽  
Gene Drives ◽  
General Method ◽  
Made In

Inheritance-biasing “gene drives” may be capable of spreading genomic alterations made in laboratory organisms through wild populations. We previously considered the potential for RNA-guided gene drives based on the versatile CRISPR/Cas9 genome editing system to serve as a general method of altering populations. Here we report molecularly contained gene drive constructs in the yeast Saccharomyces cerevisiae that are typically copied at rates above 99% when mated to wild yeast. We successfully targeted both non-essential and essential genes, showed that the inheritance of an unrelated “cargo” gene could be biased by an adjacent drive, and constructed a drive capable of overwriting and reversing changes made by a previous drive. Our results demonstrate that RNA-guided gene drives are capable of efficiently biasing inheritance when mated to wild-type organisms over successive generations.

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