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The asialoglycoprotein receptor (ASGPr) and N-acetylgalactosamine (GalNAc) is one of the most reliable receptor-ligand combinations for delivering antisense oligonucleotides (ASOs) to the liver. Here, we show that a modular GalNAc conjugation strategy allows us to reinforce the activity of the parent, naked 2′,4′-BNA/LNA gapmer targeting apolipoprotein B. The conjugation partly reduced a possible hepatotoxicity of the parent ASO. The structure-activity study revealed the significance of the metabolic susceptibility of the GalNAc moiety to nucleolytic cleavage that results in exposure of the parent gapmer. The broad usefulness of our delivery strategy of ASOs to the liver has been demonstrated. [ABSTRACT FROM AUTHOR]

Point mutations are well characterized activators of oncogenes but are often indistinguishable using common gene technologies. In general, the precise sites of point-mutated oncogenes are difficult to distinguish under physiological conditions primarily because single nucleotide mismatch do not affect the annealing temperatures of DNA probes sufficiently. To address this limitation, we developed photo-responsive oligodeoxyribonucleotides containing 2′-O-[N-(4,5′,8-trimethylpsoralen-4'-ylmethylcarbamoyl)]adenosine (Ps-amd-Oligo), which can be used to selectively manipulate and identify genes with point mutations. Here we present time course analyses of the photo-cross-linking efficiency of Ps-amd-Oligo with DNA and RNA and show promising selectivity for the oncogene H-ras. [ABSTRACT FROM AUTHOR]

By way of a brief review of Si photonics technology, we show that significant improvements in device performance are necessary for practical telecommunications applications. In order to improve device performance in Si photonics, we have developed a Si-Ge-silica monolithic integration platform, on which compact Si-Ge–based modulators/detectors and silica-based high-performance wavelength filters are monolithically integrated. The platform features low-temperature silica film deposition, which cannot damage Si-Ge–based active devices. Using this platform, we have developed various integrated photonic devices for broadband telecommunications applications. [ABSTRACT FROM AUTHOR]