Packaging cells for lentiviral vectors generated using the cumate and coumermycin gene induction systems and nanowell single-cell cloning.

Lentiviral vectors (LVs) are important for cell therapy because of their capacity to stably modify the genome after integration. This study describes a novel and relatively simple approach to generate packaging cells and producer clones for self-inactivating (SIN) LVs pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). A novel gene regulation system, based on the combination of the cumate and coumermycin induction systems, was developed to ensure tight control for the expression of cytotoxic packaging elements.

Complementary Cell Lines for Protease Gene-Deleted Single-Cycle Adenovirus Vectors.

To increase the safety of adenovirus vector (AdV)-based therapy without reducing its efficacy, a single-cycle adenovirus vector (SC-AdV) with a deletion in the protease gene (PS) was developed in order to be used as a substitute for the replication-competent adenovirus (RC-AdV). Since no infectious viral particles are assembled, there is no risk of viral shedding. The complementary cell lines for this developed AdV proved to be suboptimal for the production of viral particles and require the presence of fetal bovine serum (FBS) to grow.

Process intensification for high yield production of influenza H1N1 Gag virus-like particles using an inducible HEK-293 stable cell line.

Influenza virus dominant antigens presentation using virus like particle (VLP) approach is attractive for the development of new generation of influenza vaccines. Mammalian cell platform offers many advantages for VLP production. However, limited attention has been paid to the processing of mammalian cell produced VLPs.

Hemagglutinin and neuraminidase containing virus-like particles produced in HEK-293 suspension culture: An effective influenza vaccine candidate.

Virus-like particles (VLPs) constitute a promising alternative as influenza vaccine. They are non-replicative particles that mimic the morphology of native viruses which make them more immunogenic than classical subunit vaccines. In this study, we propose HEK-293 cells in suspension culture in serum-free medium as an efficient platform to produce large quantities of VLPs.

SHP-1 inhibits β-catenin function by inducing its degradation and interfering with its association with TATA-binding protein.

β-catenin plays a dual role both as a key effector in the regulation of adherens junctions and as a transcriptional coactivator. Tyrosine phosphorylation of β-catenin is implicated as a means for its release from E-cadherin complexes and correlates with enhanced transcriptional activity. However, it remains unclear whether or not tyrosine phosphorylated β-catenin degrades slower or faster than its unphosphorylated form or transactivates the downstream target genes differently.

The homeodomain-interacting protein kinase 2 regulates insulin promoter factor-1/pancreatic duodenal homeobox-1 transcriptional activity.

The homeodomain transcription factor insulin promoter factor (IPF)-1/pancreatic duodenal homeobox (PDX)-1 plays a crucial role in both pancreas development and maintenance of beta-cell function. Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. In humans, mutations in the IPF1 gene have been linked to diabetes.

Activation of Cdk2 stimulates proteasome-dependent truncation of tyrosine phosphatase SHP-1 in human proliferating intestinal epithelial cells.

SHP-1 is expressed in the nuclei of intestinal epithelial cells (IECs). Increased SHP-1 expression and phosphatase activity coincide with cell cycle arrest and differentiation in these cells. Suspecting the tumor-suppressive properties of SHP-1, a yeast two-hybrid screen of an IEC cDNA library was conducted using the full-length SHP-1 as bait.