Immunostimulatory and anti-neoplasm effects of a novel palindrome CpG oligodeoxynucleotide in mice.

Aim: DNAs containing unmethylated CpG motifs can stimulate innate and adaptive immunity. The aim of this study was to investigate the immunostimulatory and anti-neoplasm effects of a novel CpG oligodeoxynucleotide, ODN10, in tumor-bearing mice.

Methods: B16 melanoma-bearing C57BL/6 mice were administered ip or sc with ODN10 or conventional CpG ODN1826 on the indicated days post inoculation.

Population pharmacokinetics of rhTNFR-Fc in healthy Chinese volunteers and in Chinese patients with Ankylosing spondylitis.

Aim: To investigate the population pharmacokinetics of recombinant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR-Fc) administered via subcutaneous (SC) injection in healthy Chinese volunteers and in Chinese patients with ankylosing spondylitis (AS).

Methods: Thirty-two healthy volunteers were randomly assigned to receive a single SC injection of 12.5, 25, 37.

Optimal design and validation of antiviral siRNA for targeting hepatitis B virus.

Aim: Optimal design of antiviral short-interfering RNA (siRNA) targeting highly divergent hepatitis B virus (HBV) was validated by quantitative structure activity relationship (QSAR) analysis.

Methods: The potency of 23 synthetic siRNAs targeting 23 sites throughout HBV pregenomic RNA were evaluated at 10 nmol/L by determining the inhibition on the expression of S/P/pregenomic mRNA and hepatitis B surface antigen (HBsAg) quantitatively in HepG2.2.

Structure-efficacy relationships of immunostimulatory activity of CpG-containing oligodeoxynucleotides on mouse spleen cells.

Aim: To study the relationship between primary structures of oligodeoxynucleotides (ODN) containing unmethylated deoxycytidyldeoxyguanosine (CpG) dinucleotide motifs and their immunostimulatory activities in mouse spleen cells.

Methods: A series of CpG ODN with different primary structures were synthesized. Their capabilities to stimulate mouse spleen cell proliferation were determined by [3H]thymidine incorporation assay.

Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro.

Aim: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion.

Methods: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide.

Pharmacokinetics of His-tag recombinant human endostatin in Rhesus monkeys.

Aim: To study the pharmacokinetics and accumulation of an Escherichia coli expressed His-tag fused recombinant human endostatin (rh-endostatin) in Rhesus monkeys.

Methods: Rh-endostatin was iv or sc injected in Rhesus monkeys, and the rh-endostatin concentration in serum samples was determined by an enzyme immunoassay (EIA) method. The serum drug concentration-time data were analyzed by compartmental analysis using the practical pharmacokinetic program 3p97.

[Studies on the pharmacokinetics of lidamycin in mice and dogs using bioassay].

Aim: A bioassay method was established for the determination of active concentrations of lidamycin and studied its pharmacokinetics in mice and dogs.

Methods: Cytotoxicity of lidamycin in vitro was used to determine drug serum concentrations in vivo.

Results: Validity of methodology met the requirements of pharmacokinetic study.

Detection and quantitation of PS20, a phosphorothioate oligodeoxynucleotides in monkey plasma.

Aim: To establish the method for quantitation of the phosphorothioate oligodeoxynucleotides (S-ODNs) in plasma.

Methods: Two solid-phase extraction columns combined with a strong anion-exchange column were utilized to remove proteins and lipids in plasma, and the salts were removed by a reverse-phase column followed by dialysis with a 2500 Da-cutoff membrane. The concentration of the tested S-ODNs, PS20, and its metabolites extracted from the plasma were determined by the method of non-gel sieving capillary electrophoresis (NGCE) with diode array detection in the presence of internal standard (IS).

Optimization of antisense drug design against conservative local motif in simulant secondary structures of HER-2 mRNA and QSAR analysis.

Aim: To study the role of mRNA secondary structure stability in antisense drug design and obtain better antisense candidates against neu/HER-2/erbB-2 mRNA than previous report.

Methods: Program RNAstructure was utilized to simulate the secondary structures of HER-2 mRNA. Then 21 antisense phosphorothioate oligodeoxynucleotides (S-ODN) targeting different parts of secondary structural motif were designed.

Antisense candidates against protein kinase C-alpha designed based on phylogenesis and simulant structure of mRNA.

Aim: To optimize the antisense drug design by the combined method of phylogenetic analysis and secondary structure prediction and to get ideal candidates.

Methods: The phylogenetic analysis and the secondary structure simulation were performed by computer. Oligodeoxynucleotides (ODN) were designed against the full-conserved blocks with low local reaction free energy of protein kinase C (PKC)-alpha mRNA.

[Metabolism, Distribution and Excretion of Recombinant Human Thrombopoietin in Mice].

The metabolism, distribution and excretion profiles of recombinant human thrombopoietin (rhTPO) in mice were studied by means of (125)I-labeled rhTPO ((125)I-rhTPO) combined with size exclusive high performance liquid chromatography (SHPLC) or trichloroacetic acid (TCA) precipitation analysis. (125)I-rhTPO was prepared by iodogen method. Purification was performed on Sephacryl S-200 HR gel.

Pharmacokinetics and partial thromboplastin time after intravenous recombinant hirudin variant-2 in rhesus monkeys.

Aim: To study the pharmacokinetics (PK) and changes of kaolin partial thromboplastin time (KPTT) following single or multiple (7 d) dosing of a novel recombinant hirudin variant-2 (rHV-2) via the route of iv bolus injection (50 % of the total dose) plus infusion (the remained 50 % of the dose) in rhesus monkeys.

Methods: A crossover design was applied to research the PK and KPTT profiles of rHV-2 after single (with total dose at 1, 3, and 6 mg/kg, respectively) and multiple dosing (3 mg/kg). An enzyme-linked immunosorbent assay (ELISA) method was utilized to determine the level of rHV-2 in plasma.