Using a groundbreaking gene editing technique,
University of California scientists have created a strain of
mosquitoes capable of rapidly introducing malaria-blocking
genes into a mosquito population through its progeny,
ultimately eliminating the insects' ability to transmit the
disease to humans.
This new model represents a notable advance in the
effort to establish an antimalarial mosquito population, which
with further development could help to eradicate a disease that sickens millions worldwide each year.
To create this breed, researchers at the Irvine and San
Diego campuses inserted a DNA element into the germ line of
Anopheles stephensi mosquitoes that resulted in the gene
preventing malaria transmission being passed on to an
astonishing 99.5 percent of offspring. A. stephensi is a leading
malaria vector in Asia.
The study underlines the growing utility of the Crispr
method, a powerful gene editing tool that allows access to a cell's
nucleus to snip DNA to either replace mutated genes or insert
new ones. Results appear in the online edition of Proceedings of
the National Academy of Sciences.
"This opens up the real promise that this technique can be
adapted for eliminating malaria," said Anthony James,
Distinguished Professor of Molecular biology & Biochemistry
and Microbiology & Molecular genetics at UCI.
For nearly 20 years, the James lab has focused on
engineering anti-disease mosquitoes. His anti-dengue fever
models have been tested in cage trials in Mexico, and in 2012, he
helped to show that antibodies that impair the parasite's biology
adapted from the immune systems of mice, can be introduced
into mosquitoes. This trait, though, could only be inherited by
about half of the progeny.
Earlier this year, UC San Diego biologists Ethan Bier and
Valentino Gantz working with fruit flies announced the
development of a new method for generating mutations in both
copies of a gene. This mutagenic chain reaction involved using
the Crispr-associated Cas9 nuclease enzyme and allowed for
transmission of mutations through the germ line with an
inheritance rate of 95 percent.
The two groups collaborated to fuse Bier and Gantz's
method with James' mosquitoes. Gantz packaged antimalaria
genes with a Cas9 enzyme (which can cut DNA) and a guide
RNA to create a genetic "cassette" that, when injected into a
mosquito embryo, targeted a highly specific spot on the germ line
DNA to insert the antimalaria antibody genes.
To ensure that the element carrying the malaria-blocking
antibodies had reached the desired DNA site, the researchers
included in the cassette a protein that gave the progeny red
fluorescence in the eyes. Almost 100 percent of offspring, 99.5
percent, to be exact, exhibited this trait, which James said is an
amazing result for such a system that can change inheritable
traits.
He added that further testing will be needed to confirm
the efficacy of the antibodies and that this could eventually
lead to field studies. "This is a significant first step," said
James, a National Academy of Sciences member. "We know
the gene works. The mosquitoes we created are not the final
brand, but we know this technology allows us to efficiently
create large populations."
Bier, a Professor of Biology at UC San Diego, also noted
that "the ability of this system to carry large genetic payloads
should have broad applications to the future use of related
Crispr-based 'active genetic' systems.
An Anopheles stephensi mosquito obtains a blood meal
from a human host through its pointed proboscis. A known
malarial vector, the species can found from Egypt all the way
to China.
(Image Credit: Jim Gathany / CDC)
Malaria is one of the world's leading health problems.
More than 40 percent of the world's population live in areas
where there is a risk of contracting the disease. According to
the Centers for Disease Control & Prevention, 300 million to
500 million cases of malaria occur each year, and nearly 1
million people die of the disease annually - largely infants,
young children and pregnant women, most of them in Africa.
Source: www.sciencedaily.com
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