Tag Archives: gene drives

Living Insecticides: OX5034 Mosquito Obliterates Iteslf

A plan to release over 750 million genetically modified mosquitoes into the Florida Keys in 2021 and 2022 received final approval from local authorities, against the objection of many local residents and a coalition of environmental advocacy groups. The proposal had already won state and federal approval.

Approved by the Environment Protection Agency in May 2020, the pilot project is designed to test if a genetically modified mosquito is a viable alternative to spraying insecticides to control the Aedes aegypti. It’s a species of mosquito that carries several deadly diseases, such as Zika, dengue, chikungunya and yellow fever.  The mosquito, named OX5034, has been altered to produce female offspring that die in the larval stage, well before hatching and growing large enough to bite and spread disease. Only the female mosquito bites for blood, which she needs to mature her eggs. Males feed only on nectar, and are thus not a carrier for disease. The mosquito also won federal approval to be released into Harris County, Texas, beginning in 2021, according to Oxitec, the US-owned, British-based company that developed the genetically modified organism (GMO)…

In 2009 and 2010, local outbreaks of dengue feverleft the Florida Keys Mosquito Control District desperate for new options. Despite an avalanche of effort — from aerial, truck and backpack spraying to the use of mosquito-eating fish — local control efforts to contain the Aedes aegypti with larvicide and pesticide had been largely ineffective.
And costly, too. Even though Aedes aegypti is only 1% of its mosquito population, Florida Keys Mosquito Control typically budgets more than $1 million a year, a full tenth of its total funding, to fighting it…

The new male mosquito, OX5034, is programmed to kill only female mosquitoes, with males surviving for multiple generations and passing along the modified genes to subsequent male offspring….Environmental groups worry that the spread of the genetically modified male genes into the wild population could potentially harm threatened and endangered species of birds, insects and mammals that feed on the mosquitoes.

Excerpt from Sandee LaMotte, 750 million genetically engineered mosquitoes approved for release in Florida Keys, CNN, 

Eradicate Mosquitoes Forever: Gene Drives

The mosquitoes are being fitted with a piece of dna called a gene drive. Unlike the genes introduced into run-of-the-mill genetically modified organisms, gene drives do not just sit still once inserted into a chromosome. They actively spread themselves, thereby reaching more and more of the population with each generation. If their effect is damaging, they could in principle wipe out whole species.. If gene drives were to condemn to a similar fate the mosquitoes that spread malaria, a second of humankind’s great scourges might be consigned to history.

Gene drives can in principle be used against any creatures which reproduce sexually with short generations and aren’t too rooted to a single spot. The insects that spread leishmaniasis, Chagas disease, dengue fever, chikungunya, trypanosomiasis and Zika could all be potential targets. So could creatures which harm only humankind’s dominion, not people themselves. Biologists at the University of California, San Diego, have developed a gene-drive system for Drosophila suzukii, an Asian fruitfly which, as an invasive species, damages berry and fruit crops in America and Europe. Island Conservation, an international environmental ngo, thinks gene drives could offer a humane and effective way of reversing the damage done by invasive species such as rats and stoats to native ecosystems in New Zealand and Hawaii.

Such critics fear that the laudable aim of vastly reducing deaths from malaria—which the World Health Organisation puts at 445,000 a year, most of them children—will open the door to the use of gene drives for far less clear-cut benefits in ways that will entrench some interests, such as those of industrial farmers, at the expense of others. They also point to possible military applications: gene drives could in principle make creatures that used not to spread disease more dangerous… The ability to remove species by fiat—in effect, to get them to remove themselves—is, like the prospect of making new species from scratch, a power that goes beyond the past ambit of humankind.

Gene drives based on crispr-Cas9 could easily be engineered to target specific bits of the chromosome and insert themselves seamlessly into the gap, thus ensuring that every gamete gets a copy . By 2016, gene drives had been created in yeast, fruitflies and two species of mosquito. In work published in the journal Nature Biotechnology in September, Andrea Crisanti, Mr Burt and colleagues at Imperial showed that one of their gene drives could drive a small, caged population of the mosquito Anopheles gambiae to extinction—the first time a gene drive had shown itself capable of doing this. The next step is to try this in a larger caged population.

There are also worries about how gene drives might be used to create a weapon. …The need to find ways to guard against such attacks is one of the reasons that the Pentagon’s Defence Advanced Research Projects Agency (darpa) gives for its work on gene drives. Renee Wegrzyn, programme manager for darpa’s “Safe Genes” project, says the work is to prevent “technological surprise”, whether in the form of an unintended consequence or nefarious use. One of the academic teams she funds has made progress in developing anti-crispr enzyme systems that one day might be able to inhibit a drive’s operation.

Oversight needs not just to bring together a range of government agencies; it requires co-operation between governments, too. The Cartagena Protocol on Biosafety, which entered into force under the un Convention on Biological Diversity (cbd) in 2003, provides controls on the transfer of genetically modified organisms. But how it applies to gene drives is unclear—and besides, America has never ratified the convention. An attempt to ban gene-drive research through the cbd, which was backed by the etc Group and other ngos, failed at the convention’s biennial meeting in Cancún in 2016…Like the reintroduction of vanished species advocated by the rewilding movement, gene-drive technology will provide new arenas for the fight between those who wish to defend nature and those who wish to tame it.

Excerpts from Gene Drives: Extinction on Demand, Economist, Nov. 10, 2018, at 24

Unsafe Genes: DARPA

DARPA created the Safe Genes program to gain a fundamental understanding of how gene editing technologies function; devise means to safely, responsibly, and predictably harness them for beneficial ends; and address potential health and security concerns related to their accidental or intentional misuse. Today, DARPA announced awards to seven teams that will pursue that mission, led by: The Broad Institute of MIT and Harvard; Harvard Medical School; Massachusetts General Hospital; Massachusetts Institute of Technology; North Carolina State University; University of California, Berkeley; and University of California, Riverside. DARPA plans to invest $65 million in Safe Genes over the next four years as these teams work to collect empirical data and develop a suite of versatile tools that can be applied independently or in combination to support bio-innovation and combat bio-threats.

Gene editing technologies …[can] selectively disable cancerous cells in the body, control populations of disease-spreading mosquitos, and defend native flora and fauna against invasive species, among other uses. The potential national security applications and implications of these technologies are equally profound, including protection of troops against infectious disease, mitigation of threats posed by irresponsible or nefarious use of biological technologies, and enhanced development of new resources derived from synthetic biology, such as novel chemicals, materials, and coatings with useful, unique properties.

Achieving such ambitious goals, however, will require more complete knowledge about how gene editors, and derivative technologies including gene drives, function at various physical and temporal scales under different environmental conditions, across multiple generations of an organism. In parallel, demonstrating the ability to precisely control gene edits, turning them on and off under certain conditions or even reversing their effects entirely, will be paramount to translation of these tools to practical applications…

Each of the seven teams will pursue one or more of three technical objectives: develop genetic constructs—biomolecular “instructions”—that provide spatial, temporal, and reversible control of genome editors in living systems; devise new drug-based countermeasures that provide prophylactic and treatment options to limit genome editing in organisms and protect genome integrity in populations of organisms; and create a capability to eliminate unwanted engineered genes from systems and restore them to genetic baseline states. Safe Genes research will not involve any releases of organisms into the environment; however, the research—performed in contained facilities—could inform potential future applications, including safe, predictable, and reversible gene drives….

A Harvard Medical School team led by Dr. George Church seeks to develop systems to safeguard genomes by detecting, preventing, and ultimately reversing mutations that may arise from exposure to radiation. This work will involve creation of novel computational and molecular tools to enable the development of precise editors that can distinguish between highly similar genetic sequences. The team also plans to screen the effectiveness of natural and synthetic drugs to inhibit gene editing activity.

A North Carolina State University (NCSU) team led by Dr. John Godwin aims to develop and test a mammalian gene drive system in rodents. The team’s genetic technique targets population-specific genetic variants found only in particular invasive communities of animals. If successful, the work will expand the tools available to manage invasive species that threaten biodiversity and human food security, and that serve as potential reservoirs of infectious diseases affecting native animal and human populations….

A University of California, Berkeley team led by Dr. Jennifer Doudna will investigate the development of novel, safe gene editing tools for use as antiviral agents in animal models, targeting the Zika and Ebola viruses. The team will also aim to identify anti-CRISPR proteins capable of inhibiting unwanted genome-editing activity, while developing novel strategies for delivery of genome editors and inhibitors….

A University of California, Riverside team led by Dr. Omar Akbari seeks to develop robust and reversible gene drive systems for control of Aedes aegypti mosquito populations.

Excerpts from Building the Safe Genes Toolkit, DARPA Press Release, July 19, 2017