Horizontal Environmental Genetic Alteration Agents

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Horizontal Environmental Genetic Alteration Agents (HEGAAs) are any artificially developed agents that are engineered to edit the genome of eukaryotic species they infect when intentionally dispersed into the environment (outside of contained facilities such as laboratories or hospitals).

Contents

History

The term “genetic alteration agent” first appears in a 2016 work plan by the Defense Advanced Research Projects Agency (DARPA) describing a tender for contracts to develop genetically modified plant viruses for an approach involving their dispersion into the environment. [1] The prefixing of “horizontal environmental” to the former to generate the acronym HEGAA was first used in a 2018 scientific publication. [2] The acronym HEGAA or its plural HEGAAs has subsequently been used in scientific [3] [4] defence [5] and general media. [6] [7]

General usage

Agents such as pathogens, symbionts or synthetic protein assemblages [8] that can be acquired through horizontal transmission in the environment can potentially be engineered to become HEGAAs. This would be achieved using biotechnology methods to confer to them the capacity to alter nucleotides in the chromosomes of infected individuals through sequence-specific editing systems like CRISPR, ZFNs or TALENs. No known infectious agent naturally has the capacity to gene edit eukaryotes in a manner that can be flexibly targeted to specific sequences (distinct from substantially random natural processes like retroviral integration).

By definition, HEGAA induced gene editing events are intended to occur outside of contained facilities such as laboratories or hospitals. While genetically modified viruses with CRISPR editing have been successfully used as research tools in laboratories [9] [10] or for gene therapy in clinical settings, all gene editing events are intended to physically occur within contained facilities. By contrast, HEGAAs for their intended mode of action relies on inducing gene editing events that occur largely or exclusively in the environment.

Where HEGAAs are engineered to target obligate sexually reproducing species they can usefully be thought of being of two types:-

Where HEGAAs are engineered to target host species that can reproduce asexually, for example vegetatively reproducing plants, the above distinctions are largely no longer meaningful.

Despite an expanding number of techniques which employ engineered infectious agents to alter the genetic material of a second species, often involving genetically modified viruses, only a very small minority rely on gene editing events occurring in the environment. Furthermore, while there are a number of proposed applications which rely on the intentional dispersion of genetically modified infectious agents in the environment, only those where gene editing occurs are considered HEGAAs. Consequently, proposed applications of viral immuno-contraception, [11] [12] transmissible vaccines, [13] [14] and agricultural field transient expression systems [15] [16] are not examples of HEGAA approaches, because none currently involve gene editing. HEGAAs are only those agents that are proposed for applications that require both horizontal acquisition (infection) and gene editing events that are intended to occur in the environment.

No HEGAAs have been intentionally dispersed into the environment, though some are reportedly in development.

HEGAAs in development

Insect Allies program

Horizontal Environmental Genetic Alteration Agents is agricultural technology currently being developed by DARPA to ensure long term food security. It is under research in DARPA known as the Insect Allies project. [17] On a high level, insects serve as vectors to "infect" crops with a virus to alter their genes to become more resilient against pests, weeds and climate changes.

HEGAA like scenarios in fiction

Fictional plagues of engineered pathogens have been a feature of science fiction literature considerably prior to the advent of targetable gene editing systems. However, despite informed conjecture in media sources [18] [19] [20] or reports [21] on HEGAA like scenarios, there have been few in a fictional context.

An example of a HEGAA like scenario is a storyline in the season 10 of The X-files, with a virus engineered to contain a CRISPR system targeted to disrupt the sequence of the human adenosine deaminase gene. Gene editing of the virus is triggered in the environment as a means to destroy the human immune system in the fictional story. [22]

Related Research Articles

<span class="mw-page-title-main">Genetically modified organism</span> Organisms whose genetic material has been altered using genetic engineering methods

A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with the most common being an organism altered in a way that "does not occur naturally by mating and/or natural recombination". A wide variety of organisms have been genetically modified (GM), from animals to plants and microorganisms. Genes have been transferred within the same species, across species, and even across kingdoms. New genes can be introduced, or endogenous genes can be enhanced, altered, or knocked out.

<span class="mw-page-title-main">Genetic engineering</span> Manipulation of an organisms genome

Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA. A construct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was made by Paul Berg in 1972 by combining DNA from the monkey virus SV40 with the lambda virus. As well as inserting genes, the process can be used to remove, or "knock out", genes. The new DNA can be inserted randomly, or targeted to a specific part of the genome.

Gene knockouts are a widely used genetic engineering technique that involves the targeted removal or inactivation of a specific gene within an organism's genome. This can be done through a variety of methods, including homologous recombination, CRISPR-Cas9, and TALENs.

<span class="mw-page-title-main">Designer baby</span> Genetically modified human embryo

A designer baby is a baby whose genetic makeup has been selected or altered, often to not include a particular gene or to remove genes associated with disease. This process usually involves analysing a wide range of human embryos to identify genes associated with particular diseases and characteristics, and selecting embryos that have the desired genetic makeup; a process known as preimplantation genetic diagnosis. Screening for single genes is commonly practiced, and polygenic screening is offered by a few companies. Other potential methods by which a baby's genetic information can be altered involve directly editing the genome before birth, which is not routinely performed and only one instance of this is known to have occurred as of 2019, where Chinese twins Lulu and Nana were edited as embryos, causing widespread criticism.

Horizontal transmission is the transmission of organisms between biotic and/or abiotic members of an ecosystem that are not in a parent-progeny relationship. This concept has been generalized to include transmissions of infectious agents, symbionts, and cultural traits between humans.

Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism or in cell culture. Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect. Delivery of genes or other genetic material by a vector is termed transduction and the infected cells are described as transduced. Molecular biologists first harnessed this machinery in the 1970s. Paul Berg used a modified SV40 virus containing DNA from the bacteriophage λ to infect monkey kidney cells maintained in culture.

<span class="mw-page-title-main">Introduction to viruses</span> Non-technical introduction to viruses

A virus is a tiny infectious agent that reproduces inside the cells of living hosts. When infected, the host cell is forced to rapidly produce thousands of identical copies of the original virus. Unlike most living things, viruses do not have cells that divide; new viruses assemble in the infected host cell. But unlike simpler infectious agents like prions, they contain genes, which allow them to mutate and evolve. Over 4,800 species of viruses have been described in detail out of the millions in the environment. Their origin is unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 9,000 virus species have been described in detail of the millions of types of viruses in the environment. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. The study of viruses is known as virology, a subspeciality of microbiology.

<span class="mw-page-title-main">Genetically modified animal</span> Animal that has been genetically modified

Genetically modified animals are animals that have been genetically modified for a variety of purposes including producing drugs, enhancing yields, increasing resistance to disease, etc. The vast majority of genetically modified animals are at the research stage while the number close to entering the market remains small.

<span class="mw-page-title-main">Genetically modified virus</span> Species of virus

A genetically modified virus is a virus that has been altered or generated using biotechnology methods, and remains capable of infection. Genetic modification involves the directed insertion, deletion, artificial synthesis or change of nucleotide bases in viral genomes. Genetically modified viruses are mostly generated by the insertion of foreign genes intro viral genomes for the purposes of biomedical, agricultural, bio-control, or technological objectives. The terms genetically modified virus and genetically engineered virus are used synonymously.

<span class="mw-page-title-main">Genome editing</span> Type of genetic engineering

Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases, and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).

In biology, a pathogen in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.

<span class="mw-page-title-main">Genetic engineering techniques</span> Methods used to change the DNA of organisms

Genetic engineering techniques allow the modification of animal and plant genomes. Techniques have been devised to insert, delete, and modify DNA at multiple levels, ranging from a specific base pair in a specific gene to entire genes. There are a number of steps that are followed before a genetically modified organism (GMO) is created. Genetic engineers must first choose what gene they wish to insert, modify, or delete. The gene must then be isolated and incorporated, along with other genetic elements, into a suitable vector. This vector is then used to insert the gene into the host genome, creating a transgenic or edited organism.

<span class="mw-page-title-main">Reverse genetics</span> Method in molecular genetics

Reverse genetics is a method in molecular genetics that is used to help understand the function(s) of a gene by analysing the phenotypic effects caused by genetically engineering specific nucleic acid sequences within the gene. The process proceeds in the opposite direction to forward genetic screens of classical genetics. While forward genetics seeks to find the genetic basis of a phenotype or trait, reverse genetics seeks to find what phenotypes are controlled by particular genetic sequences.

<span class="mw-page-title-main">Gene drive</span> Way to propagate genes throughout a population

A gene drive is a natural process and technology of genetic engineering that propagates a particular suite of genes throughout a population by altering the probability that a specific allele will be transmitted to offspring. Gene drives can arise through a variety of mechanisms. They have been proposed to provide an effective means of genetically modifying specific populations and entire species.

Biotechnology risk is a form of existential risk that could come from biological sources, such as genetically engineered biological agents. The origin of such a high-consequence pathogen could be a deliberate release, an accidental release, or a naturally occurring event.

Human germline engineering is the process by which the genome of an individual is edited in such a way that the change is heritable. This is achieved through genetic alterations within the germ cells, or the reproductive cells, such as the egg and sperm. Human germline engineering is a type of genetic modification that directly manipulates the genome using molecular engineering techniques. Aside from germline engineering, genetic modification can be applied in another way, somatic genetic modification. Somatic gene modification consists of altering somatic cells, which are all cells in the body that are not involved in reproduction. While somatic gene therapy does change the genome of the targeted cells, these cells are not within the germline, so the alterations are not heritable and cannot be passed on to the next generation.

The hazards of synthetic biology include biosafety hazards to workers and the public, biosecurity hazards stemming from deliberate engineering of organisms to cause harm, and hazards to the environment. The biosafety hazards are similar to those for existing fields of biotechnology, mainly exposure to pathogens and toxic chemicals; however, novel synthetic organisms may have novel risks. For biosecurity, there is concern that synthetic or redesigned organisms could theoretically be used for bioterrorism. Potential biosecurity risks include recreating known pathogens from scratch, engineering existing pathogens to be more dangerous, and engineering microbes to produce harmful biochemicals. Lastly, environmental hazards include adverse effects on biodiversity and ecosystem services, including potential changes to land use resulting from agricultural use of synthetic organisms.

<span class="mw-page-title-main">CRISPR gene editing</span> Gene editing method

CRISPR gene editing is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.

A therapeutic interfering particle is an antiviral preparation that reduces the replication rate and pathogenesis of a particular viral infectious disease. A therapeutic interfering particle is typically a biological agent (i.e., nucleic acid) engineered from portions of the viral genome being targeted. Similar to Defective Interfering Particles (DIPs), the agent competes with the pathogen within an infected cell for critical viral replication resources, reducing the viral replication rate and resulting in reduced pathogenesis. But, in contrast to DIPs, TIPs are engineered to have an in vivo basic reproductive ratio (R0) that is greater than 1 (R0>1). The term "TIP" was first introduced in 2011 based on models of its mechanism-of-action from 2003. Given their unique R0>1 mechanism of action, TIPs exhibit high barriers to the evolution of antiviral resistance and are predicted to be resistance proof. Intervention with therapeutic interfering particles can be prophylactic (to prevent or ameliorate the effects of a future infection), or a single-administration therapeutic (to fight a disease that has already occurred, such as HIV or COVID-19). Synthetic DIPs that rely on stimulating innate antiviral immune responses (i.e., interferon) were proposed for influenza in 2008 and shown to protect mice to differing extents but are technically distinct from TIPs due to their alternate molecular mechanism of action which has not been predicted to have a similarly high barrier to resistance. Subsequent work tested the pre-clinical efficacy of TIPs against HIV, a synthetic DIP for SARS-CoV-2 (in vitro), and a TIP for SARS-CoV-2 (in vivo).

References

  1. ↑ "Broad Agency Announcement Insect Allies, Biological Technologies Office, HR001117S0002 November 1, 2016".
  2. ↑ Reeves RG, Voeneky S, Caetano-Anollés D, Beck F, Boëte C (October 2018). "Agricultural research, or a new bioweapon system?". Science. 362 (6410): 35–37. Bibcode:2018Sci...362...35R. doi:10.1126/science.aat7664. hdl: 21.11116/0000-0002-4F53-9 . PMID   30287653. S2CID   52921548.
  3. ↑ Simon S, Otto M, Engelhard M (November 2018). Sills J (ed.). "Scan the horizon for unprecedented risks". Science. 362 (6418): 1007–1008. Bibcode:2018Sci...362.1007S. doi:10.1126/science.aav7568. PMID   30498119. S2CID   54168410.
  4. ↑ Trager R (October 2018). "Pentagon's pursuit of insect-delivered genetic modification of crops prompts warnings". Chemistry World. Retrieved 2019-06-10.
  5. ↑ "Scientists: Pentagon's Plant-Virus Research Could Endanger World's Food Supply". Defense One. Retrieved 2019-06-10.
  6. ↑ Osborne H (2018-10-04). "DARPA is making insects that can deliver biological weapons, scientists have claimed". Newsweek. Retrieved 2019-06-10.
  7. ↑ "Could We Turn Insects into Biological Weapons?". American Council on Science and Health. 2018-10-17. Retrieved 2019-06-10.
  8. ↑ Butterfield GL, Lajoie MJ, Gustafson HH, Sellers DL, Nattermann U, Ellis D, et al. (December 2017). "Evolution of a designed protein assembly encapsulating its own RNA genome". Nature. 552 (7685): 415–420. Bibcode:2017Natur.552..415B. doi:10.1038/nature25157. PMC   5927965 . PMID   29236688.
  9. ↑ Ali Z, Abul-faraj A, Li L, Ghosh N, Piatek M, Mahjoub A, et al. (August 2015). "Efficient Virus-Mediated Genome Editing in Plants Using the CRISPR/Cas9 System". Molecular Plant. 8 (8): 1288–91. doi: 10.1016/j.molp.2015.02.011 . PMID   25749112.
  10. ↑ Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, et al. (April 2015). "In vivo genome editing using Staphylococcus aureus Cas9". Nature. 520 (7546): 186–91. Bibcode:2015Natur.520..186R. doi:10.1038/nature14299. PMC   4393360 . PMID   25830891.
  11. ↑ Torres JM, Sánchez C, Ramírez MA, Morales M, Bárcena J, Ferrer J, et al. (August 2001). "First field trial of a transmissible recombinant vaccine against myxomatosis and rabbit hemorrhagic disease". Vaccine. 19 (31): 4536–43. doi:10.1016/S0264-410X(01)00184-0. hdl: 20.500.12792/4539 . PMID   11483281.
  12. ↑ O'Neill G (2002). "Virus could sterilise Australia's rabbits". www.newscientist.com. Retrieved 2019-06-10.
  13. ↑ Bull JJ, Smithson MW, Nuismer SL (January 2018). "Transmissible Viral Vaccines". Trends in Microbiology. 26 (1): 6–15. doi:10.1016/j.tim.2017.09.007. PMC   5777272 . PMID   29033339.
  14. ↑ Nuismer SL, Althouse BM, May R, Bull JJ, Stromberg SP, Antia R (October 2016). "Eradicating infectious disease using weakly transmissible vaccines". Proceedings. Biological Sciences. 283 (1841): 20161903. doi:10.1098/rspb.2016.1903. PMC   5095390 . PMID   27798311.
  15. ↑ Pogue GP, Vojdani F, Palmer KE, Hiatt E, Hume S, Phelps J, et al. (June 2010). "Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems". Plant Biotechnology Journal. 8 (5): 638–54. doi:10.1111/j.1467-7652.2009.00495.x. PMID   20514694.
  16. ↑ "Southern Gardens Citrus Nursery, LLC; Notice of Intent to Prepare an Environmental Impact Statement for Permit for Release of Genetically Engineered Citrus tristeza virus". www.regulations.gov. Retrieved 2019-06-10.
  17. ↑ "DARPA Enlists Insects to Protect Agricultural Food Supply and Commodity Crops". www.darpa.mil.
  18. ↑ Brooks R. "Can There Be War Without Soldiers?". Foreign Policy. Retrieved 2019-06-10.
  19. ↑ Regalado A. "Top U.S. Intelligence Official Calls Gene Editing a WMD Threat". MIT Technology Review. Retrieved 2019-06-10.
  20. ↑ Block S (1999). Living nightmares: Biological warfare threats enabled by molecular biology. In The New Terror: Facing the Threat of Biological and Chemical Weapon . Hoover Institution Press. ISBN   978-0817997014.
  21. ↑ Hauck DJ (2005). "Pandora's Box Opened Wide: UAVs Carrying Genetic Weapons". RAND Corp. Archived from the original on June 1, 2022.
  22. ↑ "CRISPR patent belongs to aliens : A view From the Bridge". blogs.nature.com. Retrieved 2019-06-10.
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