Researchers have successfully created a genetically engineered mosquito that shows a high level of resistance against the most prevalent type of dengue fever virus, providing a powerful weapon against a disease that infects 50 million people each year.
Anthony James, a UC Irvine vector biologist, is one of a team of researchers who injected DNA into mosquito embryos, creating the first stable transgenic mosquito resistant to Type 2 dengue fever virus, the most prevalent strain of the disease. The mosquitoes that survived the procedure also remained fertile and were able to reproduce, a key factor for any future strategies that may involve replacing mosquito populations with their genetically modified counterparts.
The results were published this week in the early online edition of the Proceedings of the National Academy of Sciences.
"These results are very exciting because they provide us a genetic tool we can use to control mosquito-borne diseases such as dengue fever," James said. "We have been working for some time on the individual components of creating a genetically modified mosquito that would fend off dengue infection, but this is the first time we have brought all the pieces together to create a stable model that can also reproduce."
In the study, the researchers exploited a vulnerability of the dengue virus to make the mosquitoes resistant to infection. This vulnerability occurs when the virus replicates and its single strand of RNA - a chemical cousin of DNA - briefly becomes double-stranded. At this point, the virus is vulnerable because of a naturally occurring protein called dicer-2. This protein initially has no effect on a single strand of RNA, but acts like scissors on the double strand, chopping it up and rendering its genetic material useless. Once this process is started, the single-stranded RNA also becomes vulnerable to dicer-2 and is cut up, thereby preventing further virus replication.
On its own, this process of self-destruction happens only after the virus has already replicated and been transmitted; however, the researchers found a way to control and speed up the process. They accomplished this by cloning a section of the virus' RNA and injected two inverse copies of it into mosquito embryos. The copies formed a double-stranded RNA, which, as expected, bound with dicer-2 and was chopped up. The virus never had the opportunity to replicate. As a result, they could "inoculate" mosquitoes with a form of the virus that would essentially be benign.
Joining James on the study, funded by a 2001 grant from the National Institutes of Health, were researchers from Colorado State University and from Virginia Polytechnic Institute and State University.