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