By Christen Brownlee
Science News, 1/29/2007
Straight to the Source
Scottish
scientists have genetically engineered hens that can not only produce
useful drugs in their eggs but also reliably pass on this
characteristic to new generations of chickens. Successfully combining
these two traits represents a first for researchers aiming to transform
animals into living drug factories, the scientists say.
Certain proteins can counteract a variety of medical
conditions, from anemia to diabetes to cancer. While some of these
protein drugs are relatively simple to make in the lab, others are
difficult, time-consuming, or expensive to produce.
Since animals naturally make thousands of proteins, researchers
have sought to harness this innate capability. Over the past several
years, scientists have engineered cows, sheep, and other mammals to
produce protein drugs.
However, these animals have several drawbacks, says Simon
Lillico of the Roslin Institute outside Edinburgh. Most of the
engineered animals are large, expensive to house and feed, and take
years to mature enough to produce the desired proteins. Furthermore,
these animals can't stay healthy while making compounds toxic to
mammalian cells—a trait many medicines require.
Some researchers have suggested that chickens—with their small
sizes, low maintenance needs, and quick generation times—could produce
protein drugs in their eggs. But Lillico notes that previous attempts
to engineer drug-producing chickens have run into problems. For
example, in some engineered hens, drug-making capability fades with
each generation.
Lillico and his colleagues, led by the Roslin Institute's Helen
Sang, took a new approach. They constructed drug-coding genes that
would insert themselves into the gene that all chickens carry for
making the egg-white component ovalbumin.
The team worked with two synthetic genes that code for
different protein drugs: an antibody called miR24, which has shown
promise against melanoma, and a protein called human
interferon-beta-1a, which is already used to treat multiple sclerosis.
The researchers employed viruses to ferry both genes into cells in
young chick embryos inside unhatched eggs.
When the eggs hatched, the researchers selected the male chicks
that carried the altered gene. When the team later bred these roosters
with normal hens, half the female offspring laid eggs containing both
protein drugs in their whites, the researchers report in an upcoming
Proceedings of the National Academy of Sciences.
The researchers continue to screen for male offspring carrying the
genes and to breed them with normal hens. They now have five
generations of drug-producing birds, Lillico says.
The newly engineered chickens "could pave the way to something
very interesting," says animal sciences professor François Pothier of
Laval University in Quebec City, who has engineered pigs to produce
useful proteins in their semen. Pothier points out that before chickens
roost in pharmaceutical factories, the researchers in Scotland have
many hurdles to overcome, such as increasing the small amounts of the
two drugs present in the hens' egg whites.
However, Pothier notes that once the scientists perfect their
technique, it might be possible to introduce a variety of useful
proteins that would improve eggs' food value.
"You can imagine that eventually, not only could you modify the
content of an egg for therapeutics, but you could perhaps change the
flavor or add something interesting for health," such as vitamins or
heart-healthy fatty acids, Pothier says.