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The use of chemically synthesized short interfering RNAs (siRNAs) is currently the method of choice to manipulate gene expression in mammalian cell culture, yet improvements of siRNA design is expectably required for successful application in vivo. Several studies have aimed at improving siRNA performance through the introduction of chemical modifications… (More)
BACKGROUND Reperfusion injury is a vital problem in non-heart-beating donor (NHBD) organs. The sodium-hydrogen inhibitor cariporide is thought to improve cellular integrity after ischemia and reperfusion. Recently, we demonstrated the possibility of preserving hearts with in situ perfusion after circulatory death. The purpose of this study was to determine… (More)
A non-heart-beating donor model was considered to examine whether pig hearts from the abattoir could be resuscitated by whole blood reperfusion. For preservation, machine perfusion using University of Wisconsin (UW) solution was compared with storage on ice. Nineteen hearts from abattoir pigs, harvested 25 +/- 3 min after exsanguination, were harvested and… (More)
We recently reported that a 1'-deoxy-1'-(4,6-difluoro-1H-benzimidazol-1-yl)-2'-(beta-aminoethyl)-beta-d-ribofuranose nucleoside appears to be a universal nucleoside which does not differentiate between the four natural nucleosides A, C, G, and U in duplexes. Moreover, ribozymes modified with this nucleoside analog showed a better or at least equal catalytic… (More)
Chemical synthesis has been a major endeavor to create active siRNAs. The downregulation of mRNA by 21-mer double-stranded siRNAs can be improved by using modified nucleotides, especially 2'-O-alkylated ones. Besides the commercially available 2 cent-O-methyl ribosides, 2'-alkyl groups bearing positive charges are especially promising candidates. We have… (More)
Here we report a novel synthetic pathway for an efficient modification of RNA-oligonucleotides on solid-support using universal nucleosides bearing a 2'-O-aminopropyl-tether.
BACKGROUND Organ shortage limits the number of transplantations, and donor deterioration may precede and often prevent conventional organ preservation. This study evaluates in situ perfusion as a bedside method for cardiac allograft procurement in a large animal model. METHODS Thirty Landrace pigs (42 +/- 7 kg) were studied. The hearts in the conventional… (More)