Oligonucleotides Which Specifically Bind Retroviral Nucleocapsid Proteins
Background:
The Retroviral Replication Lab at
the National Cancer Institute is seeking statements of capability,
or interest, from parties interested in collaborative research to
further develop, evaluate, and/or commercialize oligonucleotides
which bind retroviral nucleocapsid proteins with high affinity.
The human immunodeficiency virus (HIV) is the causative agent of
acquired immunodeficiency syndrome (AIDS). A retroviral protein
species, the gag polyprotein, is involved in the assembly of
retrovirus particles and capable of specific interactions with
nucleic acids. After the virion is released from the cell, the
polyprotein is cleaved by the virus-encoded protease. One of the
cleaved products, the nucleocapsid (NC) protein, then binds to
genomic RNA, forming the ribonucleoprotein core of the mature
particle. It has been hypothesized that the NC protein is capable
of binding to any single-stranded nucleic acid under appropriate
conditions. The protein plays crucial roles in both the reverse
transcription and integration steps in the viral life
cycle.
Technology:
This invention describes
oligonucleotides which bind retroviral nucleocapsid proteins. The
technology is based on the surprising discovery that retroviral
nucleocapsid proteins, such as NC and the gag precursor have the
ability to bind to specific nucleic acid sequences with extremely
high affinity. The high affinity of this interaction has potential
applications in the design of new antiviral approaches and in
sensitive detection of HIV particles. Accordingly, the invention
provides for molecular decoys for retroviral nucleocapsid proteins
which inhibit viral replication, targeted molecules comprising high
affinity oligonucleotides, assays for selecting test compounds, and
related kits.
Further R&D
Needed:
More work is needed to devise antiviral
strategies based on the high-affinity interaction we have
described.
R&D Status:
Development is continuing, including a detailed analysis of the
interaction of HIV-1 NC protein with the described oligonucleotides
and an extension of the analysis to larger HIV-1 proteins
containing NC.
IP Status:
U.S. Patent No. 6,316,190 issued 13 Nov 2001
Value
Proposition--Solution:
- Assays and test kits for sensitive detection of HIV
particles
- Development of antiviral compounds and novel methods for
inhibiting HIV viral replication
Contact
Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov
Reference: #605 KH
Posted 01/11/2008
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