Antisense Therapeutic Agents for Treatment of Covid-19

Case ID:
OSU-20-33
Web Published:
9/9/2020
Description:

Technology Description

This technology licensing opportunity relates to antisense agent compounds for treating or preventing a SARS-CoV-2 infection. A key feature of this technology is unique cell penetrating peptide and antisense oligomer (CPP-PMO) combinations that provide improved antiviral efficacy and reduced cytotoxicity. The compounds are oligomers that comprise nucleic acid base sequence antisense directed to the genomic RNA sequence of SARS-CoV-2, a backbone comprising moieties that sterically block DNA or RNA cleavage, and a peptide. In a recent study, five PPMOs targeted against various sites in the genomic RNA of SARS-CoV-2, along with a negative control PPMO, were evaluated for their ability to suppress virus growth in cell cultures. Each PPMO was tested for its effect on the viability of uninfected cells and its inhibitory effect on the replication of SARS-CoV-2 in Vero cell cultures. Cell viability was evaluated with an ATP-based method and viral growth was measured with quantitative RT-PCR and TCID50 infectivity assays. In cell viability assays, cells treated with PPMO at the concentrations used in the antiviral assays described below for 48 hours showed no loss of viability. In the antiviral assays, cells were treated with 4, 8 or 16 µM PPMO for 5 hours, then infected and further incubated without PPMO. The cells were assayed for viral titer at various time points post-infection. Four of the five PPMOs were highly efficacious, reducing viral titers by up to 4-6 log10 at 48-72 hours post-infection, in a non-toxic and dose-responsive manner. The data indicate that PPMOs can potently and specifically suppress SARS-CoV-2 growth and are promising candidates for further pre-clinical development. We suggest that further in vitro and in vivo evaluations are warranted.

Background of Invention

SARS-CoV-2 (Family: Coronaviridae) is the causative agent of COVID-19. Development of innovative direct-acting antiviral agents is sorely needed to address this virus. Peptide-conjugated morpholino oligomers (PPMOs) are antisense agents composed of a phosphordiamidate morpholino oligomer covalently conjugated to a cell-penetrating peptide. PPMOs require no delivery assistance to enter cells and can reduce expression of targeted RNA through sequence-specific steric blocking.

Status

A U.S. provisional patent application is on file at the USPTO. The technology is available for exclusive or non-exclusive licensing. The pending patent application is co-owned with the Federal Government.

   

 

Patent Information:
Category(s):
Therapeutics
For Information, Contact:
Joe Christison
IP & Licensing Manager
Oregon State University
541-737-9016
joe.christison@oregonstate.edu
Inventors:
David Stein
Hong Moulton
Kyle Rosenke
Heinrich Feldmann
Keywords:
antisense
coronavirus
covid-19
Drug
SARS-CoV-2
Therapeutic
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