Researchers are exploring the use of the revolutionary gene-editing tool CRISPR-Cas9 to fight human disease along with agricultural blight. although a study via Indiana University has found several challenges to the method’s use in saving lives along with crops.
The research, reported today inside journal Science Advances, combines advanced genetic along with statistical analyses to show how certain genetic along with behavioral qualities in disease-carrying insects, like mosquitoes, make these species resistant to genetic manipulation.
which resistance could complicate attempts to use CRISPR-Cas9 inside fight against malaria—a deadly mosquito-borne disease which threatens over 3 billion people worldwide—or crop blights such as the western corn rootworm, an invasive species which costs the U.S. about $1 billion in lost crops each year.
The discovery of the CRISPR-Cas9 system—or simply “CRISPR”—inside early 2010s introduced an unprecedented level of accuracy in genetic editing. Scientists can use the method to design highly precise genetic “scissors” which snip out along with replace specific parts of the genome with sequences of their choosing. Two English scientists were the first to show the method could spread infertility in disease-carrying mosquitoes in late 2015.
“We found which tiny genetic variation within species—as well as many insects’ tendency to inbreed—can seriously impact the effectiveness of attempts to reduce their numbers using CRISPR technology,” said Michael J. Wade, Distinguished Professor of Biology at IU Bloomington. “Although rare, these naturally occurring genetic variants resistant to CRISPR are enough to halt attempts at population control using genetic technology, quickly returning wild populations to their earlier, ‘pre-CRISPR’ numbers.”
which means costly along with time-consuming efforts to introduce genes which could control insect populations—such as a trait which causes female mosquitoes to lay fewer eggs—would likely disappear in a few months. which is usually because male mosquitoes—used to transmit brand new genes since they don’t bite—only live about 10 days.
The protective effect of naturally occurring genetic variation is usually strong enough to overcome the use of “gene drives” based on CRISPR-based technology—unless a gene drive is usually matched to the genetic background of a specific target population, Wade added. Gene drives refer to genes which spread at a rate of nearly 0 percent—significantly higher than the normal 50 percent chance of inherence which occurs in sexually reproducing organisms.
Wade, an expert in “selfish genes” which function similarly to gene drives due to their “super-Darwinian” ability to rapidly spread throughout a population, teamed up with colleagues at IU—including Gabriel E. Zentner, an expert in CRISPR-based genetic tools along with assistant professor inside Department of Biology—to explore the effectiveness of CRISPR-based population control in flour beetles, a species estimated to destroy 20 percent of the planet’s grain after harvest.
The team designed CRISPR-based interventions which targeted three segments inside genome of the flour beetle via four parts of the planet: India, Spain, Peru along with Indiana. They then analyzed the DNA of all four varieties of beetle along with found naturally occurring variants inside targeted gene sequence, the presence of which would likely impact the effectiveness of the CRISPR-based technology.
The analysis revealed genetic variation in all four species at nearly every analyzed DNA segment, including a variance rate as high as 28 percent inside Peruvian beetles. Significantly, Wade’s statistical analysis found which a genetic variation rate as low as 1 percent—combined having a rate of inbreeding typical to mosquitos inside wild—was enough to eliminate any CRISPR-based population-control methods in six generations.
The results suggest which a careful analysis of genetic variation inside target population must precede efforts to control disease-carrying insects using CRISPR technology. They also suggest which the unintended spread of modified genes across the globe is usually highly unlikely since typical levels of genetic variation place a natural roadblock on spread between regions or species.
“Based on which study, anyone trying to reduce insect populations through which method should conduct a thorough genetic analysis of the target gene region to assess variation rates,” Wade said. “which will help predict the effectiveness of the method, as well as provide insight into ways to circumvent natural genetic variation through the use of Cas9 variants with an altered sequence specificity.”
Modifying fat content in soybean oil with the molecular scissors Cpf1
D.W. Drury el al., “CRISPR/Cas9 gene drives in genetically variable along with nonrandomly mating wild populations,” Science Advances (2017). http://advances.sciencemag.org/content/3/5/e1601910 , DOI: 10.1126/sciadv.1601910