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Genetic engineering tools that propagate genes within a target species have the potential to humanly control pests and eradicate parasitic diseases such as malaria.
The tools, known as genetic readers, ensure that the modified organisms transmit the desired genetic variants to their offspring. These variants could for example ensure that organisms produce only male offspring or sterile females.
In this way, genetic keys could be used to exterminate insects such as mosquitoes carrying pathogens, likely to spread malaria, dengue and Zika virus. Gene readers could also be used to control invasive species such as rodents that may threaten the survival of native animals.
However, previously described versions of gene readers based on the CRISPR genome editing system have the potential to spread far more widely than their intended local population – and to affect an entire species. The effects could also extend beyond international borders, potentially leading to disputes between countries where no prior agreement has been reached.
These types of problems could significantly delay, if not completely prevent, the security of testing and the introduction of the technology.
Now, in an article published today in the Proceedings of the National Academy of Sciences, researchers at MIT and Harvard University describe a gene control system with integrated controls.
CRISPR-based training consists of a series of chain-linked genetic elements, according to Kevin Esvelt, an badistant professor of media arts and sciences and head of the Sculpting Evolution research group at MIT Media Lab, who led the research.
A link within the daisy control system encodes the CRISPR gene editing system itself, while each of the other links encodes for the guide RNA sequences. These guidance sequences tell the CRISPR system to cut and copy the next link in the chain, says Esvelt.
The addition of additional links allows the daisy system to spread for additional generations within the population.
"Imagine that you have a chain of daisies and that in each generation you take away the one at the end. Esvelt explains that when you run out of hardware, the daisy chain connection stops.
In this way, a small number of genetically engineered organisms could be released into the wild to propagate the daisy shoot within the local population and then stop when they have been programmed.
"We are programming the body to edit the CRISPR genome alone, within its reproductive cells, at each generation," says Esvelt.
Esvelt developed the system in collaboration with George Church, Professor of Genetics at Harvard Medical School, Visiting Professor at the Media Lab, and Senior Associate Member of the Broad Institute of MIT and Harvard. The co-primary authors, Charleston Noble and John Min, both graduates of Harvard Medical School, led modeling and molecular biology experiments designed to ensure system stability, respectively.
"If we want the world to take advantage of new gene-inducing technologies, we need to be very confident that we can reverse and contain it, both theoretically and through controlled testing," said Church.
"Many applications of gene drives involve islands and other geographical isolation, at least for initial testing, including invasive species and Lyme disease," he noted. "It would be good for these highly motivated local governments to carry out tests that do not automatically affect adjacent islands or metropolises. Garland discs offer this. "
The research suggests that for every 100 wild-type counterparts, the release of a single modified organism with a three-chain chain control system, once per generation, should be enough to alter the entire population in about two generations. , about a year in a fast environment. reproductive insect. This compares to existing systems that need to release at least as many organisms as those that already exist in a local population, and sometimes 10 to 100 times more.
The process could take several years in species that breed more slowly, such as mice, but would be more humane than the current use of rodenticides, which can also harm humans and predatory species, says Esvelt.
In 2014, Esvelt and his colleagues first suggested that CRISPR-Cas9 could be used in gene control systems, and he felt morally responsible for developing an alternative to self-propagating systems, says -he. "Ideally, localization will allow each community to make decisions about its own environment, without imposing these decisions on others.
According to Prof. Luke Alphey, head of arthropod genetics at the Pirbright Institute in the UK, self-propagating transmission systems can spread rapidly within target populations. However, such training systems are also likely to extend to all connected populations of the target species – which is desirable if you want to change the entire set of species. kind, undesirable if you do not, he says.
"Daisy campaigns potentially offer a way to get the most out of these genes, while limiting the spread and limiting the persistence of these genes, even within the target population," says Alphey. "This is probably very desirable when you want to reach one population but not another of the same species, perhaps an invasive population of pests, but not populations of the same species in its natural range."
Alphey was not involved in initial research on daisy drive, but is now collaborating with Esvelt, particularly on work related to the use of daisy drive in mosquitoes.
Esvelt and the Sculpting Evolution group are also beginning to explore the potential use of this technology to hereditarily immunize white-footed mice, the main reservoir of the bacteria that causes Lyme disease in North America. They are also setting up a research collaboration to explore the use of daisies in CochliomyieAlso known as the New World worm, a parasitic fly that produces larvae that devour living tissue from warm-blooded animals, causing considerable suffering.
In addition, researchers are also studying this technology for use in nematode worms, microscopic creatures that breed every three days. This will allow them to conduct evolving laboratory studies of organisms modified by the daisy process, with the goal of ensuring that systems can not spread autonomously.
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