The method consists of delivering instances of the specific RNA
structural elements (called the decoy), in single copy or multiple copies, into
a cell. A range of delivery methods
could be employed, including but not limited to RNA transfection and viral
transduction/phage infection. In
cases where the introduction of external RNA may have deleterious consequences
(as in mammalian cells), the RNAs can be modified by the addition of 5' CAP and
3' poly-A tail. Once inside the
cell, these decoys will compete with endogenous targets of the RNA-binding
protein for binding and therefore, in effect, displace the RNA-binding protein
from its native sites throughout the genome. This decoy-titration process has
the effective consequence of reducing the function of the specific RNA-binding
protein that recognizes the decoy. The efficacy of this RNA-decoy titration
knock-down effect can be monitored by assaying for the relevant RNA behavior of
the native targets of the RNA-binding protein. For example, if the function of
the RNA-binding protein is to stabilize mRNAs, the RNA-decoy titration
knock-down would be expected to decrease the stability of the
targets.
This RNA-decoy titration knock-down technology
is
a versatile approach for modulating the function of RNA-binding proteins and is
complementary to siRNA/shRNA knockdown.
Applications
For targeting and interfering with the function of an
RNA-binding protein
·
As a
therapeutic
·
In industrial
settings
Advantages
·
Versatile
·
Specific
·
Complementary to siRNA/shRNA
knockdown
Intellectual Property and Commercialization
Strategy
A
provisional application has been filed.
Princeton is interested in identifying partners for further development
and commercialization of this technology
A Novel Method for Modulating Cell Proliferation Rate
for
Clinical, Industrial and Research
Applications
Princeton Docket #
12-2796-C
Through biochemistry, mass spectrometry and in vivo binding studies, Princeton
researchers identified human HNRPA2B1 (heterogeneous nuclear ribonucleoprotein
A2/B1) as the key regulator that binds sRSM1 and stabilizes a large number of
its target genes. Modulation of
HNRPA2B1 resulted in a significant
change in proliferation rate in human cancer cells lines. Thus, manipulation of this protein can be
applied to alter cell proliferation in any clinical and/or industrial
settings.
Advantage
Novel mechanism
Applications
Modulation of cellular proliferation by interfering
with HNRPA2B1 for
·
Clinical applications including
treating
o Cancer
o Non-neoplastic endothelial tissue diseases
(arteriosclerosis, proliferative retinal disorders, hemangioma, cheloids,
fibrosis, etc.)
·
Industrial applications
including
o Synthetic
biology
o Biotechnological
engineering
Intellectual Property and Commercialization
Strategy
A
provisional application has been filed.
Princeton is interested in identifying partners for further development
and commercialization of this technology
Publication
Goodarzi H, Najafabadi HS, Oikonomou P, Greco TM, Fish L, Salavati R,
Cristea IM, Tavazoie S. Systematic discovery of structural elements governing
stability of mammalian messenger RNAs.
Nature. (2012) doi:
10.1038/nature11013.
Inventors
Saeed
Tavazoie is
Professor of Biochemistry and Molecular Biophysics in Columbia University.
The
focus of his research is to understand the organizing principles that
underlie the evolution and function of molecular networks. Prof. Tazazoie¿s honors include a CAREER
Award from the National Science Foundation and NIH Director¿s Pioneer
Award.
Hani
Goodarzi is
a postdoctoral fellow in Prof. Tavazoie¿s lab at Columbia University.
