Pharmacokinetics of IDX184, a liver-targeted oral prodrug of 2'-methylguanosine-5'-monophosphate, in the monkey and formulation optimization for human exposure.

IDX184 is a phosphoramidate prodrug of 2'-methylguanosine-5'-monophosphate, developed to treat patients infected with hepatitis C virus. A mass balance study of radiolabeled IDX184 and pharmacokinetic studies of IDX184 in portal vein-cannulated monkeys revealed relatively low IDX184 absorption but higher exposure of IDX184 in the portal vein than in the systemic circulation, indicating >90 % of the absorbed dose was subject to hepatic extraction. Systemic exposures to the main metabolite, 2'-methylguanosine (2'-MeG), were used as a surrogate for liver levels of the pharmacologically active entity 2'-MeG triphosphate, and accordingly, systemic levels of 2'-MeG in the monkey were used to optimize formulations for further clinical development of IDX184.

Amplified electrocatalysis at DNA-modified nanowires.

Arrayed gold nanowires are a novel and useful platform for electrochemical DNA detection. Pilot studies testing the use of these templated structures with an electrocatalytic reporter system revealed that very low detection thresholds for target DNA sequences can be obtained. One factor contributing to the heightened sensitivity is the high signal-to-noise ratio achieved with the large electrocatalytic signals observed at DNA-modified nanowires.

Ultrasensitive electrocatalytic DNA detection at two- and three-dimensional nanoelectrodes.

Electrochemical DNA detection systems are an attractive approach to the development of multiplexed, high-throughput DNA analysis systems for clinical and research applications. We have engineered a new class of nanoelectrode ensembles (NEEs) that constitute a useful platform for biomolecular electrochemical sensing. High-sensitivity DNA detection was achieved at oligonucleotide-functionalized NEEs using a label-free electrocatalytic assay.

DNA-functionalized nanotube membranes with single-base mismatch selectivity.

We describe synthetic membranes in which the molecular recognition chemistry used to accomplish selective permeation is DNA hybridization. These membranes contain template-synthesized gold nanotubes with inside diameters of 12 nanometers, and a "transporter" DNA-hairpin molecule is attached to the inside walls of these nanotubes. These DNA-functionalized nanotube membranes selectively recognize and transport the DNA strand that is complementary to the transporter strand, relative to DNA strands that are not complementary to the transporter.