Publications by authors named "H K Tewary"

Part I of this review has already been presented on methods of processing and purification of crude or raw samples in cell-culture or cell free systems. Part II of the review focuses on the in vivo models of determination of input oligonucleotides in both non-primates and primates. Emphasis has been given to the techniques developed for quantification of oligonucleotides or their metabolites from biological samples including blood, plasma, serum, urine and other tissues.

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Part I of this review attempts to bring together all the methods of detection and determination of synthetic oligonucleotides used in in vitro, described in the literature over the past 14 years, in an effort by scientists to use these oligonucleotides as drugs in gene therapy. The in vitro models include cell-free and cell culture systems. Emphasis has been given to the techniques developed for quantification of the input oligonucleotides or their metabolites.

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Current therapy for acute myelogenous leukemia (AML) includes induction with Ara-C and an anthracycline, such as daunorubicin, idarubicin, or mitoxantrone. Unfortunately, most patients relapse from initial remission. Nearly one-fifth of early relapses experience treatment-related deaths.

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Phosphorothioate oligonucleotides (PS-ODN) designed to temporarily modulate selected gene expression have made the journey from bench top to beside in a remarkably short period of time. A PS-ODN with sequence complementary to the p53 mRNA was administered to mice (4 mg/kg subcutaneously), rats (3-300 mg/kg intravenously), monkeys (intravenous infusions for up to 15 days) and humans (up to 0.25 mg/kg/h intravenous infusions for 10 days).

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Phosphorothioate oligonucleotides (S-ODNs) have the ability to modulate gene expression selectively and thus have potential therapeutic capabilities. This potential led us to investigate the protein binding characteristics of selected S-ODNs. We evaluated S-ODN interactions with bovine serum albumin (BSA) and human serum albumin (HSA) in vitro.

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