Peptide-phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics that bind and silence gene targets. Through designing PPMOs that silence essential or resistance genes in pathogens, these antisense oligomers could be utilized as novel antimicrobials. Towards this end, my thesis employed minimum inhibitory concentration assays (MICs) to identify PPMOs capable of...
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...
Morpholino oligos (Morpholinos) are widely used tools for knocking down gene expression and are currently in a clinical trial for treatment of Duchene muscular dystrophy. A Morpholino analog has been in a clinical trial as a potential anti-bioterrorism agent for inhibiting replication of deadly Marburg viral infection. The cellular uptake...
Exon skipping is capable of correcting frame-shift and nonsense mutations of
Duchenne Muscular Dystrophy (DMD). Phase II clinical trials in UK and Netherlands
have reported induction of dystrophin expression in muscles of DMD patients by
systemic administrations of both phosphorodiamidate morpholino oligomers (PMO)
and 2’O methyl phosphorothioate. Peptide-conjugated PMO (PPMO)...
Hepatitis E virus (HEV) infection is a cause of hepatitis in humans worldwide. Recently, persistent and chronic HEV infections have been recognized as a serious clinical problem, especially in immunocompromised individuals. To date, there are no FDA-approved HEV-specific antiviral drugs. In this study, we designed and evaluated antisense peptide-conjugated morpholino...
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...
Bovine viral diarrhea virus (BVDV) is an enveloped, single-stranded positive-sense RNA virus. The BVDV genome is about 12.5 kb long and consists of a single open reading frame (ORF) flanked by untranslated regions at the 5' and 3' ends (5'-UTR and 3'- UTR, respectively). To investigate the role of cis-sequences...
Humans and viral disease are inextricably intertwined. Viral disease plays an immeasurable role in human life, from the disease and economic burden associated with every facet of contending with human viral disease, to managing the consequences of viral disease in organisms important to our food supply, economy, and entertainment. The...
Antisense morpholino oligomers are synthetic macromolecules can modify gene expression. While these compounds have great potential to treat a broad range of human diseases, they suffer from poor cellular delivery. Conjugating cell-penetrating peptides onto these morpholinos is one option of addressing delivery, however development remains slow due to the cost...
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 -...