Researchers at UC Berkeley and UC Riverside have merged computational and molecular biology to demonstrate the potential that gene modification may have in suppressing mosquito-borne diseases.
Published recently in Nature journal’s Scientific Reports, the research uses CRISPR-Cas9 technology to successfully interrupt a gene required for female fertility in fruit flies. If replicable in mosquito populations, the technology would have potential to suppress the spread of diseases carried by mosquitos such as dengue, malaria, chikungunya and Zika virus.
“In some senses, the mosquito is the animal in human history that’s killed the most people,” said campus professor of biostatistics and statistics Nicholas Jewell. “Mosquito-borne infections put an incredible disease burden on the world.”
CRISPR is a gene-editing technique pioneered by campus professor of chemistry, biochemistry and molecular biology Jennifer Doudna, in which specific DNA sequences are located by RNA guides that send Cas9 proteins to bind to and cut the DNA: essentially turning off the chosen DNA sequence.
“Something new like CRISPR comes along and it changes things,” said John Marshall, lead author of the study and campus assistant professor of biostatistics and epidemiology. “In this case, it sped things up.”
Initially, researchers found that when utilizing a single RNA guide, the population bounces back because mutations occur and a resistant allele is generated, Marshall said. The study’s breakthrough was multiplexing — a technique that uses multiple RNA guides to tag multiple DNA sites to then be modified.
“From one guide RNA … we expected to suppress a population of 32 mosquitos,” Marshall said. “Our calculations suggest that if you were to tag four at once, the frequency at which you were to get mutation would be so rare that you can potentially suppress a population equal to the continent of Africa.”
Omar Akbari, one of the authors of the study and an assistant professor of entomology at UC Riverside, successfully demonstrated the multiplexing technique in fruit flies, Marshall said. Marshall Lab then mathematically modeled the implications of the findings.
Marshall said the technology has a lot of potential to control diseases because, unlike other malaria prevention techniques such as bed nets or anti-malarial drugs, gene-editing mosquitos does not require human compliance. Marshall said in addition to modeling the spread of the technology into a population, he is also working on modeling control and remediation techniques.
“We need to be really careful that we proceed in a thoughtful way,” Marshall said. “(This means) respecting the local communities that would be exposed to the technology, making sure we do risk assessments to ensure that it’s safe and has the intended effects and respecting the regulatory authorities and the Convention on Biological Diversity.”