Characterization of integration frequency and insertion sites of adenovirus DNA into mouse liver genomic DNA following intravenous injection.

While generally referred to as "non-integrating" vectors, adenovirus vectors have the potential to integrate into host DNA via random, illegitimate (nonhomologous) recombination. The present study provides a quantitative assessment of the potential integration frequency of adenovirus 5 (Ad5)-based vectors following intravenous injection in mice, a common route of administration in gene therapy applications particularly for transgene expression in liver. We examined the uptake level and persistence in liver of first generation (FG) and helper-dependent (HD) Ad5 vectors containing the mouse leptin transgene.

Lack of effects on fertility and developmental toxicity of a quadrivalent HPV vaccine in Sprague-Dawley rats.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases, with approximately half of the HPV-infected people being adolescents and young adults. A recently developed quadrivalent HPV vaccine, GARDASIL((R)), has been shown to be highly effective in the prevention of a number of HPV-mediated diseases. The objective of the present study was to evaluate the potential effects of the vaccine on female fertility and F1 development, growth, behavior, and reproductive performance.

Ensuring the quality, potency and safety of vaccines during preclinical development.

There is an abundance of vaccines currently in development, with most of them exploring novel mechanisms, adjuvants and/or delivery systems not only for traditional prophylactic use, but also for therapeutic uses. As vaccines are generally administered to healthy individuals, ensuring their quality, potency and safety becomes crucial, especially prior to evaluation in humans. To ensure these key attributes, vaccine developers need to incorporate them as early in the development program as possible, starting in basic research and continuing through preclinical, clinical and postmarketing development.

Peroxisome proliferators activate growth regulatory pathways largely via peroxisome proliferator-activated receptor alpha-independent mechanisms.

Peroxisome proliferators (PPs) induce liver tumors in rodents through an unknown mechanism requiring PP-activated receptor (PPAR) alpha. Since PPs possess growth modulatory activities that may be important to their hepatocarcinogenicity, we aimed at dissociating the activation of growth signaling pathways from the PPARalpha-mediated response induced by PPs in cultured rat primary hepatocytes. Pretreatment with the differentiation-promoting agent dimethylsulfoxide (DMSO) increased PPARalpha mRNA/protein and enhanced the expression of PPARalpha-regulated genes [fatty acyl Co-A oxidase (FACO), cytochrome P450 4A1 (CYP4A1)] induced by PPs.