CONTACT: Chaoyong Ma, Ph.D.
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PHYLONIX GRANTED U.S. PATENT FOR HIGH THROUGHPUT
DRUG SCREENING USING ZEBRAFISH
Cambridge, MA (March 30, 2004) - Phylonix today announced the recent award
of Patent No. 6,656,449 "Methods of Screening Agents for Activity Using
Teleosts" by the United States Patent and Trademark Office which includes
claims for performing drug screening on zebrafish using microtiter plates.
This high throughput format permits development of quantitative in vivo
bioassays, which is not possible with other vertebrate animal models.
Other key claims also include performing drug screening for toxicity,
apoptosis, and angiogenesis using zebrafish.
"This is important recognition of our pioneering efforts to develop both
visual and quantitative methods for drug screening, target identification,
and target validation using zebrafish as a model organism," said Patricia
McGrath, President & CEO. Corresponding patent applications for this
subject matter have been filed in major international markets, including
Europe and Asia.
Laboratory animals are critical for defining the mechanisms of drug
activity and for testing therapeutic regimens, however, only a few useful
models have been developed. Zebrafish has several important advantages for
drug screening: they are small, inexpensive to maintain and easily bred in
large numbers. Eggs are externally fertilized and a single mating produces
100-200 eggs. Single embryos can be maintained in fluid volumes as small
as 100 microliters for the first six days of development and cultured in
microtiter wells. Chemicals can then be added directly to the fish water,
permeating the intact embryo. Microliters of drug are required for
zebrafish compared with milliliters per mouse. Standard microtiter plate
readers can be used for measurement, making this format particularly
attractive for high throughput drug screening.
An important advantage of the zebrafish animal model is that the
morphological and molecular bases of tissue and organ development are, in
general, either identical or similar to other vertebrates, including man.
The zebrafish completes embryogenesis in 120 hours and most of the
interenal organs, including the gut, liver, kidney, and heart develop
rapidly in the first 48-72 hours. This rapid development allows organ
toxicity and specific drug effects to be assayed in a comparatively short
time frame. The sequence and presumed function of many genes that are
important for development in vertebrates have been conserved in zebrafish.
The cloning of zebrafish orthologues of important mammalian genes has
been greatly facilitated by the creation of an EST database containing
tens of thousands of clones for which sequences are available through
Whole embryo testing has previously been performed on invertebrates,
including fruitfly and nematode, however, these organisms are not closely
related to humans and they lack many of the same organs and enzymes.
Therefore, their use as comparative models for toxicity effects in humans
is limited. All essential components of vertebrate form and organ
development are mimicked in the transparent zebrafish and their molecular
basis is either identical or similar, underscoring the potential for use
in research on human diseases.
Phylonix Pharmaceuticals, Inc. is a Contract Research Organization focused
on developing and marketing novel in vivo zebrafish based assays for
therapeutic and industrial screening for cancers, central nervous system
and cardiovascular diseases, apoptosis, and organ toxicity. The Company
has assembled embryo and chemical sample handling instrumentation to
automate analysis. The Company has established a state of the art
aquaculture facility that can produce thousands of embryos per week.
Initially, the Company offers services for drug screening, primarily to
the pharmaceutical industry. Long term, the Company expects to contribute
to the study and treatment of human diseases by genetic screening, gene
cloning, and target identification using zebrafish as a model system.