Novel HIV Therapeutic Approach: Targeting APOBEC-3G(A3G):RNA Complexes

Brief Description:

APOBEC-3G (A3G) is a cytidine deaminase enzyme that interferes with the replication of HIV and other retroviruses by mutating viral nucleic acids, thus playing an important role in innate anti-viral immunity. Viral infectivity factor (Vif) is a protein found in HIV and other retroviruses which disrupts the antiviral activity of the A3G by targeting it for ubiquitination and cellular degradation. Conventional therapies against the HIV virus are targeting Vif to prevent Vif-dependent degradation of A3G. However, protection of A3G from Vif does not necessarily mean that A3G will be active because cellular RNAs bind to it and force it into aggregates that are inactive. 

 

Applications:

The therapeutic development of antiviral compounds that activate A3G host defense by liberating RNA from A3G in living cells. This was done using a quenched FRET high-throughput screening (HTS) assay with in vitro recombinant A3G:RNA complexes to identify these “hit” compounds dissociating A3G from RNA. Hits from the HTS have been validated as having antiviral activity and function as antagonists of RNA binding to A3G.

 

Advantages:

Targeting A3G:RNA complexes is a novel therapeutic approach to activate A3G host defense to attack virus as they enter cells and thereby inhibit HIV replication and integration. It does not have resistance issues associated with present HIV therapeutics.

URV Reference Number: 6-1934
Patent Information:
Category(s):
Therapeutic
For Information, Contact:
Matan Rapoport
Licensing Associate
University of Rochester
585.276.6600
matan.rapoport@rochester.edu
Inventors:
Harold Smith
Kimberly Prohaska
William McDougall
Keywords:
AIDS
Antiviral
HIV
Infectious Disease
Therapy
Viral disease