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Principal Investigator:
David E. Levy, Ph.D., Department of Pathology, NYU School of Medicine
Joan E. Durbin, MD, Ph.D., Children's Hospital Research Foundation, Wexner, Ohio
Adolfo Garcia-Sastre, Ph.D., Mt. Sinai School of Medicine
Peter Palese, Ph.D., Mt. Sinai School of Medicine
Background
Interferons (IFNs) are cytokines that produce antiviral responses in cells. Both
type I (IFNs a and ß) and type II IFN (IFN g ) treatment of cells leads
to the activation of a family of proteins termed signal transducers and
activators of transcription, or STATs. There are multiple members of the STAT
family. IFNs a and ß induction of cells leads to the phosphorylation of
both STAT1 and STAT2, whereas IFN g stimulation of cells only phosphorylates STAT1.
In addition to the activation by the IFN system, STAT1 is also activated by a
variety of cytokines and growth factors, including IL-6, leukemia inhibitory factor
(LIF), oncostatin M, growth hormone, IL-10, epidermal growth factor (EGF), platelet
derived growth factor (PDGF), colony stimulating factor 1 (CSF1) and angiotensin
II. Transgenic mice in which STAT1 gene is disrupted appear to be normal at birth,
but they are extremely prone to viral infections. These mice do not respond to
IFN treatment by mounting an antiviral response.
Description
Dr. Levy, and colleagues have derived permanent cell lines from these STAT1 deficient
mice that are very susceptible to viral infections and are able to grow viruses
to very high titers. The cell lines are also much more sensitive to infection
and therefore are capable of detecting and amplifying small quantities of virus.
The inventors have derived the cell lines from a number of different strains of
mice in which the STAT1 gene is ablated. Both primary and immortalized lines have
been derived, including oncogene-transformed lines. The cell lines obtained do
not respond to IFN either from an exogenous source or endogenously produced IFN,
and therefore do not develop an antiviral response. These attributes make these
cells useful for a number of applications.
Applications
These cell lines can be exploited for a number of purposes. One is the production
of virus stocks for vaccines. There are limitations in the current technology
for growing ample viral stocks. Influenza virus is currently produced in embryonated
chicken eggs, which is a problem for people allergic to eggs. Another use of these
cell lines is in utilizing them to grow high titers of recombinant virus vectors
(e.g., for gene therapy). Yet another application is in viral diagnosis. STAT1
deficient cell lines could be used to detect extremely low levels of virus present
in clinical samples. These lines could amplify the virus titer thus facilitating
diagnosis
Patent Status
A U.S. patent application has been filed covering this novel
technology.
For further information
please contact
New York University
Industrial Liaison/Technology Transfer
650 First Avenue, New York, N.Y. 10016
Tel: (212)263-8178 Fax: (212)263-8189
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