Index Catalog // ScholarsArchive@OSU

The development of broad-spectrum antiviral medical countermeasures to treat viral hemorrhagic fevers caused by natural or weaponized virus infections

Creator:: Hickman, Mark R., Saunders, David L., Bigger, Catherine A., Kane, Christopher D., and Iversen, Patrick L.
Abstract:: The Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO-CBRND) began development of a broad-spectrum antiviral countermeasure against deliberate use of high-consequence viral hemorrhagic fevers (VHFs) in 2016. The effort featured comprehensive preclinical research, including laboratory testing and rapid advancement of lead molecules into nonhuman primate (NHP)...
Resource Type:: Article

AVI-7288 for Marburg Virus in Nonhuman Primates and Humans

Creator:: Heald, Alison E., Charleston, Jay S., Iversen, Patrick L., Warren, Travis K., Saoud, Jay B., Al-Ibrahim, Mohamed, Wells, Jay, Warfield, Kelly L., Swenson, Dana L., Welch, Lisa S., Sazani, Peter, Wong, Michael, Berry, Diane, Kaye, Edward M., and Bavari, Sina
Abstract:: BACKGROUND: AVI-7288 is a phosphorodiamidate morpholino oligomer with positive charges that targets the viral messenger RNA that encodes Marburg virus (MARV) nucleoprotein. Its safety in humans is undetermined. METHODS: We assessed the efficacy of AVI-7288 in a series of studies involving a lethal challenge with MARV in nonhuman primates. The...
Resource Type:: Article and Presentation

A Single Phosphorodiamidate Morpholino Oligomer Targeting VP24 Protects Rhesus Monkeys against Lethal Ebola Virus Infection

Creator:: Warren, Travis K., Whitehouse, Chris A., Wells, Jay, Welch, Lisa, Heald, Alison E., Charleston, Jay S., Sazani, Pete, Reid, St. Patrick, Iversen, Patrick L., and Bavari, Sina
Abstract:: Ebola viruses (EBOV) cause severe disease in humans and nonhuman primates with high mortality rates and continue to emerge in new geographic locations, including several countries in West Africa, the site of a large ongoing outbreak. Phosphorodiamidate morpholino oligomers (PMOs) are synthetic antisense molecules that are able to target mRNAs...
Resource Type:: Article

Induced IL-10 Splice Altering Approach to Antiviral Drug Discovery

Creator:: Panchal, Rekha G., Mourich, Dan V., Bradfute, Steven, Hauck, Laura L., Warfield, Kelly L., Iversen, Patrick L., and Bavari, Sina
Abstract:: Ebola virus causes an acute hemorrhagic fever lethal in primates and rodents. The contribution of host immune factors to pathogenesis has yet to be determined and may reveal efficacious targets for potential treatment. In this study, we show that the interleukin (IL)-10 signaling pathway modulates Ebola pathogenesis. IL-10 [superscript -...
Resource Type:: Article

Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies

Creator:: Heald, Alison E., Iversen, Patrick L., Saoud, Jay B., Sazani, Peter, Charleston, Jay S., Axtelle, Tim, Wong, Michael, Smith, William B., Vutikullird, Apinya, and Kaye, Edward
Abstract:: Two identical single-ascending-dose studies evaluated the safety and pharmacokinetics (PK) of AVI-6002 and AVI-6003, two experimental combinations of phosphorodiamidate morpholino oligomers with positive charges (PMOplus) that target viral mRNA encoding Ebola virus and Marburg virus proteins, respectively. Both AVI-6002 and AVI-6003 were found to suppress disease in virus-infected nonhuman primates...
Resource Type:: Article

Benzimidazoisoquinolines: a new class of rapidly metabolized aryl hydrocarbon receptor (AhR) ligands that induce AhR-dependent Tregs and prevent murine graft-versus-host disease

Creator:: Punj, Sumit, Kopparapu, Prasad, Jang, Hyo Sang, Phillips, Jessica L., Pennington, Jamie, Rohlman, Diana, O'Donnell, Edmond, Iversen, Patrick L., Kolluri, Siva Kumar, and Kerkvliet, Nancy I.
Abstract:: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays multiple roles in regulation of immune and inflammatory responses. The ability of certain AhR ligands to induce regulatory T cells (Tregs) has generated interest in developing AhR ligands for therapeutic treatment of immune-mediated diseases. To this end, we...
Resource Type:: Article

Gene-silencing antisense oligomers inhibit Acinetobacter growth in vitro and in vivo

Creator:: Geller, Bruce L., Marshall-Batty, Kimberly, Schnell, Frederick J., McKnight, Mattie M., Iversen, Patrick L., and Greenberg, David E.
Abstract:: Background: Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA/RNA analogs that silence expression of specific genes. We studied whether PPMOs targeted to essential genes in Acinetobacter lwoffii and A. baumannii are active in vitro and in vivo. Methods: PPMOs were evaluated in vitro using MIC and viability assays, and in...
Resource Type:: Article

Bacterial Resistance to Antisense Peptide-Phosphorodiamidate Morpholino Oligomers

Creator:: Puckett, Susan E., Reese, Kaleb A., Mitev, Georgi M., Mullen, Valerie, Johnson, Rudd C., Pomraning, Kyle R., Mellbye, Brett L., Tilley, Lucas D., Iversen, Patrick L., Freitag, Michael, and Geller, Bruce L.
Abstract:: Peptide phosphorodiamidate morpholino oligomers (PPMO) are synthetic DNA mimics that bind complementary RNA and inhibit bacterial gene expression. (RFF)₃RXB- AcpP PPMO (R, arginine; F, phenylalanine; X, 6-aminohexanoic acid; B, β-alanine) is complementary to 11 bases of the essential gene acpP (encodes acyl carrier protein). The MIC of (RFF)₃RXB-AcpP was 2.5...
Resource Type:: Article

Lymphocytic Choriomeningitis Virus Infection in FVB Mouse Produces Hemorrhagic Disease

Creator:: Schnell, Frederick J., Sundholm, Sarah, Crumley, Stacy, Iversen, Patrick L., and Mourich, Dan V.
Abstract:: The viral family Arenaviridae includes a number of viruses that can cause hemorrhagic fever in humans. Arenavirus infection often involves multiple organs and can lead to capillary instability, impaired hemostasis, and death. Preclinical testing for development of antiviral or therapeutics is in part hampered due to a lack of an...
Resource Type:: Article

Calicivirus (Genus Vesivirus) associated with post-transfusional hepatitis

Creator:: Smith, Alvin, Kurth, Andreas, Skilling, Douglas E., Smith, Chet C., Iversen, Patrick L., Bok, Karen, and Matson, David O.
Abstract:: Peer reviewed for presentation. This is the abstract and PowerPoint slides for a presentation made at the 26th Annual Meeting of the American Society for Virology held at Oregon State University in Corvallis, Oregon from July 14 - 18, 2007.
Resource Type:: Presentation

ScholarsArchive@OSU

The development of broad-spectrum antiviral medical countermeasures to treat viral hemorrhagic fevers caused by natural or weaponized virus infections

AVI-7288 for Marburg Virus in Nonhuman Primates and Humans

A Single Phosphorodiamidate Morpholino Oligomer Targeting VP24 Protects Rhesus Monkeys against Lethal Ebola Virus Infection

Induced IL-10 Splice Altering Approach to Antiviral Drug Discovery

Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies

Benzimidazoisoquinolines: a new class of rapidly metabolized aryl hydrocarbon receptor (AhR) ligands that induce AhR-dependent Tregs and prevent murine graft-versus-host disease

Gene-silencing antisense oligomers inhibit Acinetobacter growth in vitro and in vivo

Bacterial Resistance to Antisense Peptide-Phosphorodiamidate Morpholino Oligomers

Lymphocytic Choriomeningitis Virus Infection in FVB Mouse Produces Hemorrhagic Disease

Calicivirus (Genus Vesivirus) associated with post-transfusional hepatitis

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