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5-Animals: Genetically engineered mosquitoes show resistance to dengue fever virus



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TITLE:  Genetically engineered mosquitoes show resistance to dengue fever
        virus
SOURCE: Univeristy of California - Irvine
        http://today.uci.edu/news/release_detail.asp?key=1448
DATE:   08 Mar 2006

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Genetically engineered mosquitoes show resistance to dengue fever virus
Researchers create new tool against transmission of virus

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.

James and his colleagues performed tests on a family of mosquitoes
descended from one of the original embryos that survived the procedure.
They found that the vast majority of that family was highly resistant to
dengue infection. They also were able to detect the engineered RNA in the
mosquitoes, a sign that the genetic alteration had been successful and
passed down through reproduction. Furthermore, when that genetic
modification was reversed, the mosquitoes were as susceptible to the
virus as they had been before the procedure.

Dengue fever is endemic in more than 100 countries in Africa, the
Americas, the Eastern Mediterranean, Southeast Asia and the Western
Pacific. The virus is transmitted to people by mosquitoes of the species
Aedes aegypti. The World Health Organization estimates 50 million cases
of dengue infection each year. Approximately 20,000 people die annually
from the disease.

James, a professor of microbiology and molecular genetics, and of
molecular biology and biochemistry, has made a number of significant
advances on genetic approaches to interrupt malaria parasite and dengue
virus transmission by mosquitoes. He has received a number of
international awards for his research.

In 2005, he received a $19.7 million grant from the Foundation for the
National Institutes of Health to lead an international effort to develop
new methods to control the transmission of dengue fever. The project is
among 43 groundbreaking research projects to improve health in developing
countries, supported by $436 million for the Grand Challenges in Global
Health Initiative, launched by the Bill and Melinda Gates Foundation.

According to James, the next step of this research will be to use the
FNIH grant to explore population replacement strategies using the
genetically modified mosquitoes. He stressed that no genetically altered
mosquitoes will be released at any time during these studies.

About the University of California, Irvine: The University of California,
Irvine is a top-ranked university dedicated to research, scholarship and
community service. Founded in 1965, UCI is among the fastest-growing
University of California campuses, with more than 24,000 undergraduate
and graduate students and about 1,400 faculty members. The second-largest
employer in dynamic Orange County, UCI contributes an annual economic
impact of $3.3 billion. For more UCI news, visit www.today.uci.edu.




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