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Crispr Deployed to Stop Disease, Pest Insects

Nikolay Kandul and Omar Akbari

Nikolay Kandul, left, and Omar Akbari (University of California in San Diego)

9 Jan. 2019. A genetics lab is using the genome editing technique Crispr to create sterilized male insects, which can lead to fewer disease-spreading and farm pest insects. A team led by University of California in San Diego biologist Omar Akbari describes the technique in yesterday’s issue of the journal Nature Communications.

Akbari’s lab studies genetic methods for controlling insects, particularly those spreading infectious diseases, including mosquitoes responsible for public health threats such as yellow fever, zika, dengue fever, and malaria. The lab does much of its research with model insect organisms, such as fruit flies — known formally as Drosophila — which have genomes similar to a range of insect species. These fruit flies, however, are also pests harming cherry crops in California and elsewhere.

The lab’s current work includes adapting the genome editing technique Crispr, short for clustered regularly interspaced short palindromic repeats, to disrupt the reproduction of insects, to minimize or stop the birth of offspring. Crispr is a genome-editing process based on bacterial defense mechanisms that use RNA to identify and monitor precise locations in DNA. The actual editing of genomes with Crispr employs enzymes that cleave DNA strands at the desired points, with Crispr-associated protein 9, or Cas9, being the enzyme used for the longest period.

Interrupting insect reproduction patterns has a long history, going back to the 1950s. Those earlier methods, known as the sterile insect technique, use radiation to sterilize male insects in a target population, causing the eventual collapse of entire insect communities. Later techniques use genetic engineering to stop reproduction functions in males and females. These later techniques require altering specific genes in the genomes of target insects, which can vary from one species to another, essentially requiring a customized solution with each use. In addition, they require successive generations of insects to mate and reproduce before the target population collapses.

The UC-San Diego researchers designed a process with Crispr called precision-guided sterile insect technique, which they say is more efficient and applicable to a wider range of insect species than current radiation and genetic engineering methods. The use of Crispr for the lab’s precision-guided technique was developed by research scientist and first author Nikolay Kandul, and creates altered strains of the target species, where the genes governing fertility and sex determination are excised.

In lab tests, the team genetically edited the fruit flies, where females produced only sterile males, which the researchers replicated in large numbers of insects. The result, say the researchers is a much faster collapse of the target population. Moreover, the edited genomes affect only the fruit flies’ reproductive functions. The male insects are otherwise fit, allowing them to compete for female mates. The researchers say the genes edited by the precision-guided sterile insect technique are found in a wide range of insects. Using statistical models, the team says its techniques would reduce disease-spreading or farm pest insect populations faster than current techniques.

The researchers envision producing genetically edited species in labs and shipping the altered insects to communities or farms where they’re needed. “This is a novel twist of a very old technology,” says Kandul in a university statement. “That novel twist makes it extremely portable from one species to another species to suppress populations of mosquitoes or agricultural pests, for example those that feed on valuable wine grapes.”

The university applied for a provisional patent, essentially an intent to file for a patent, on the technology. Akbari is a co-founder of the start-up company Agragene Inc. in Carlsbad, California formed to commercialize the process.

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