Investigating synthetic oligonucleotide targeting of miR31 in Duchenne muscular dystrophy

Exon-skipping via synthetic antisense oligonucleotides represents one of the most promising potential therapies for Duchenne muscular dystrophy (DMD), yet this approach is highly sequence-specific and thus each oligonucleotide is of benefit to only a subset of patients. The discovery that dystrophin mRNA is subject to translational suppression by the microRNA miR31, and that miR31 is elevated in the muscle of DMD patients, raises the possibility that the same oligonucleotide chemistries employed for exon skipping could be directed toward relieving this translational block. This approach would act synergistically with exon skipping where possible, but by targeting the 3’UTR it would further be of benefit to the many DMD patients who express low levels of in-frame transcript. We here present investigations into the feasibility of combining exon skipping with several different strategies for miR31-modulation, using both in vitro models and the mdx mouse (the classical animal model of DMD), and monitoring effects on dystrophin at the transcriptional and translational level. We show that despite promising results from our cell culture model, our in vivo data failed to demonstrate similarly reproducible enhancement of dystrophin translation, suggesting that miR31-modulation may not be practical under current oligonucleotide approaches. Possible explanations for this disappointing outcome are discussed, along with suggestions for future investigations

Injection of a drag-reducing fluid into turbulent pipe flow of a Newtonian fluid

Injection of drag reducing fluid into turbulent pipe flow of Newtonian flui

Saturn orbiter mission study

A preliminary analysis of the important aspects of missions orbiting the planet Saturn is provided. Orbital missions to Saturn is given serious consideration for the 1980's, or after flybys by Pioneer 10/G and Mariner Jupiter-Saturn 1977. An attempt is made to characterize Saturn orbiters in detail so that comparisons with Jupiter missions can be made. The scientific objectives of Saturn exploration are grouped under four topics: (1) the atmosphere, (2) the magnetosphere, (3) the rings, and (4) the satellites

Study of the mechanics of non-Newtonian fluids Final report, 26 Jun. 1963 - 26 Dec. 1968

Aspects of mechanics of nonNewtonian fluid

Effects of spiral longitudinal vortices on turbulent boundary layer skin friction

Effect of spiral longitudinal vortices on turbulent boundary layer skin frictio

Wind-tunnel investigation of the aerodynamic pressures on the Apollo command module configuration

Wind tunnel study of aerodynamic pressures on Apollo command module configuratio