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Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer
  • Bo Wu, H. Moulton, +11 authors Qi Long Lu
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences
  • 30 September 2008
TLDR
Systemic delivery of the novel PPMO restores dystrophin to almost normal levels in the cardiac and skeletal muscles in dystrophic mdx mouse, leading to increase in muscle strength and prevents cardiac pump failure induced by dobutamine stress in vivo. Expand
Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice.
TLDR
PPMO M23D-B, designed to force skipping of stop-codon containing dystrophin exon 23, is investigated in an mdx mouse model of Duchenne muscular dystrophy, the first report of oligonucleotide-mediated exon skipping and dystrophic protein induction in the heart of treated animals. Expand
Advanced antisense therapies for postexposure protection against lethal filovirus infections
TLDR
Administration of positively charged phosphorodiamidate morpholino oligomers (PMOplus), delivered by various dosing strategies initiated 30–60 min after infection, protects >60% of rhesus monkeys against lethal Zaire Ebola virus (ZEBOV) and 100% of cynomolgus monkeysagainst Lake Victoria Marburg virus (MARV) infection. Expand
Cellular uptake of antisense morpholino oligomers conjugated to arginine-rich peptides.
TLDR
It is shown that conjugation to arginine-rich peptides significantly enhanced the cellular uptake of PMO and R(9)F(2)C was best suited to deliver a PMO to its target RNA resulting in the strongest antisense effect. Expand
Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents.
TLDR
Mechanistic investigations about its uptake mechanisms lead to the conclusion that these three vectors are internalized using the same endocytic route involving proteoglycans, but that the (R-Ahx-R)(4)-PMO(705) conjugate has the unique ability to escape from lysosomial fate and to access to the nuclear compartment. Expand
West Nile virus genome cyclization and RNA replication require two pairs of long-distance RNA interactions.
TLDR
The 5'UAR/3' UAR pairing may release the 3' end of viral genome (as a template) during the initiation of minus-strand RNA synthesis, but not for viral translation. Expand
Treatment of AG129 mice with antisense morpholino oligomers increases survival time following challenge with dengue 2 virus
TLDR
PPMO had considerable antiviral efficacy against DENV-2 in the AG129 mouse model and that PPMO treatment early in the course of an infection was critical to extending the survival times of DENv-2-infected mice in theAG129 model system. Expand
Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
TLDR
A combination of EBOV-specific PMOs targeting sequences of viral mRNAs for the viral proteins (VPs) VP24, VP35, and RNA polymerase L protected rodents in both pre- and post-exposure therapeutic regimens. Expand
Lipoxygenase inhibitors abolish proliferation of human pancreatic cancer cells.
TLDR
The current studies indicate that both 5- LOX and 12-LOX expression is upregulated in human pancreatic cancer cells and LOX plays a critical role in Pancreatic cancer cell proliferation. Expand
Inhibition of Flavivirus Infections by Antisense Oligomers Specifically Suppressing Viral Translation and RNA Replication
TLDR
The results suggest that antisense PMO-mediated blocking of cis-acting elements of flavivirus genomes can potentially be developed into an anti-flavivirus therapy. Expand
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