DISSOLVING BUGS FOR BIOTECH DRUGS
By Sean Henahan, Access Excellence
ITHACA, N.Y. (9/30/97)- Liquefied lepidotera larvae may prove
to be a very productive source of recombinant proteins, thanks to a new
biotechnology technique.
Researchers at Cornell University's Boyce Thompson Institute for Plant
Research modified a technique called HeRD (high-efficiency rearing device),
originally developed for use in biological pest control, by which caterpillar
larvae attach to rows of small pillars, making it easy to infect them with
viruses that produce valuable therapeutic proteins.
 Caption:
A HeRD system box about the size of a shoe box can raise thousands of tiny
insect larvae. Photo by Patrick Hughes, BTI.
The technique involves infecting the larvae with genetically engineered
baculoviruses. Baculovirus is a class of insect virus that has been used to make DNA cloning vectors
for gene expression in eukaryotic cells. The advantage of the baculovirus
system is that it produces proteins that are glycosylated, although the
glycosylation may differ somewhat from that produced in a mammalian system.
In addition, expression levels are relatively high, making it a useful
vector for the production of recombinant proteins.The virus attacks the
inside of the larvae, altering its metabolism and killing it. Immediately
before the insect dies, the recombinant protein of choice is harvested
and refined into a pharmaceutical product.
"These are valuable proteins, and they can't be produced this well any
other way," said H. Alan Wood, a virologist at BTI. "Essentially, this
is a protein factory. We are using insects to raise raw pharmaceutical
proteins. In effect, we are turning insects into little protein factories."
The new technique represents an improvement on a more expensive and
time-consuming method using recombinant baculoviruses to produce pharmaceutical
proteins in insect cell cultures.
The virus spreads through the caterpillar within 24 hours, but the bug
continues to grow, spreading virus through the caterpillar's body for three
days. Just prior to the fourth day, or the fifth larval stage, the proteins
being grown in the bug are ready for harvest. If the protein is not harvested
from the caterpillar during this crucial larval stage, the proteins are
destroyed.
The HeRD system was developed following the observation that insects
prefer getting their footing on the edges of surfaces, not directly on
flat surfaces. The system is basically a box full of close-spaced pillars
shaped like small popsicle sticks, with bugs and food added. The insects
are reared on the pillars in the box, making it easy to infect them with
baculovirus and then harvest the proteins.
The recombinant baculovirus can now be used for producing vaccines against
a number of diseases including human papillomavirus, human T-cell leukemia
virus, hepatitis-C virus, Norwalk virus, rotavirus, porcine parvovirus
and African swine fever virus.
The new technologies could also be used for other purposes, such as
manufacturing inexpensive viral insecticides as alternatives to pesticides.
With more than 30,000 chemical pesticide registrations being canceled in
the past eight years, there is a need to develop natural and genetic baculoviruses,
the researcher note.
The research appears in the July 24, 1997, edition of the journal Entomophaga,
the publication of the International Organization for Biological Control
of Noxious Animals and Plants.
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