November 19, 2015

Promise and Peril of Gene drive

The idea sounds appealingly simple: Quickly spread a gene through a population of animals in order to prevent it from transmitting disease, or, more directly, to kill a destructive species such as an agricultural pest. Gene-drive technology is at the heart of such concepts. Gene drive shifts biases inheritance to favor certain versions of genes, a genetic alteration introduced into a few members of a population spreads rapidly throughout the entire population. If that alteration inhibits reproduction or survival in some way, gene drive can drive that population extinct in theory. In other uses, a desired trait could be driven through a population.

In July, geneticists showed that one gene drive system was almost 100% effective in spreading a mutated pigmentation gene through a population of lab fruit flies, fueling fears about the power of gene drive.

There are a number of reasons why gene drives may not be as useful, or scary, as some think:

  • Gene drive works only in sexually reproducing species, and the genetic change spreads further with each successive generation. So changing or eliminating a population is practical only if the species has a short generation time—like Drosophila, or mosquitos. With many vertebrates, it would take decades for an introduced gene mutation or trait to spread wide enough to make a difference.
  • It has not yet been demonstrated that a CRISPR-Cas9 gene-driven change persists across many generations. The paper where gene drive was so effective only reported on one generation. For mosquitos, in which researchers want to knock out populations near people or introduce a parasite-resistant gene, modeling efforts indicate that drive would have to persist 20 generations to spread completely, Burt says.
  • There are few, if any, organisms so well characterized, say biologists, that they can predict the ecological effect of a gene-driven change or a disappearing population. We will “have the ability not just to change the genome but [also] to change the balance of species in a community,” says Allison Snow, a plant biologist from Ohio State University, Columbus. “There’s a lot of potential for ignorance, human error, or intent to cause harm.”
  • Before gene drive can be applied to wild populations instead of well-characterized laboratory ones, the CRISPR-Cas9 genome–editing technology needs to become even more precise. As Shengdar Tsai, a CRISPR researcher at Massachusetts General Hospital in Boston, pointed out, his team’s analysis of the method in human cells uncovered about two dozen so-called off-target effects—places where the DNA not meant to be changed was. The sites identified confirm that the sites affected by CRISPR-Cas9 can be difficult to predict.
  • Instead of using gene drive to make malaria-carrying mosquitos extinct, a less ecologically worrisome strategy would be to change the insect’s genome so it would not transmit the malaria parasite to humans. But researchers don’t know enough about the mosquito immune system to target a specific gene for this type of gene drive yet, Burt says.
  • An effective “fail-safe” strategy that would cause gene drive to peter out after a specified number of generations or because researchers decide they needed to stop a gene’s spread still needs to be developed. One of the more promising ones—to undo the genetic change with another gene drive effort—may still be problematic if it’s gene drive itself that goes awry.
  • Hybridization between closely related animal species needs to be better understood before gene drives are unleashed. Successful mating between two species results in so-called gene flow, which could allow a gene-driven mutation to hop into an unintended species. This could be useful for malaria control—a gene drive given to one parasite-carrying mosquito species could spread it to the other seven that carry the human pathogen. But in other scenarios, a species-hopping gene drive could lead to the demise of the wrong species.

SOURCE - Journal Science by Elizabeth Pennisi

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