Xenobiotic exposures may induce alternative splicing in the pre-mRNA of nuclear hormone receptor (NHR) genes, yielding unpredictable patterns of gene expression that may promote adverse drug events and promote environmental disease. Informed by observations in the androgen receptor (AR; class I NHR), whereby alternatively-spliced AR transcripts induce ligand-independent hormone signaling...
Cutaneous melanoma remains the deadliest form of skin cancer arising from malignant transformation of pigment-producing melanocytes, with a diagnosis of metastasis indicating a median survival rate of less than a year. Solar ultraviolet (UV) radiation, especially childhood sun exposure, is an important etiological risk factor of melanoma. This DNA damage...
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...
Full Text:
Nonhuman Primates and Humans
Alison E. Heald, M.D., Jay S. Charleston, Ph.D., Patrick L. Iversen, Ph.D
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...
Full Text:
., Patrick L. Iversen, Ph.D.,
Travis K. Warren, Ph.D., Jay B. Saoud, Ph.D., Mohamed Al-Ibrahim, M.B., Ch.B
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...
Full Text:
Information Section 1.
1. Given Name (First Name)
Patrick
2. Surname (Last Name)
Iversen
4. Are you the
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...
Full Text:
, Charleston JS, Iversen PL, et al. AVI-7288 for Marburg virus in nonhuman primates
and humans. N Engl J Med
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...
Full Text:
, Iversen PL, et al. AVI-7288 for Marburg virus in nonhuman primates and
humans. N Engl J Med 2015;373:339
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)...
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...
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...