118 research outputs found
Field Production and Functional Evaluation of Chloroplast-Derived Interferon-α2b
Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-α2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-α2b for the treatment of hepatitis C infection is $26 000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-α2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-α2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-α2b had similar in vitrobiological activity to commercially produced PEG-Intron™ when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-α2b were also seen in vivo . Chloroplast-derived IFN-α2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-α2b purified from chloroplast transgenic lines (cpIFN-α2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-α2b, transgene containment and biological activity akin to that of commercial preparations of IFN-α2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization
Assessment of cell proliferation and prognostic factors in canine mammary gland tumors
Improved siRNA-mediated silencing in refractory adherent cell lines by detachment and transfection in suspension
Effect of Bleomycin Scheduling on Lung Metastases of 3LL and a Subline of Different Metastatic Potential
Selective Expression of Nonsecreted Interferon by an Adenoviral Vector Confers Antiproliferative and Antiviral Properties and Causes Reduction of Tumor Growth in Nude Mice
Intracellular activation of tumoricidal properties in mouse macrophages and human monocytes by recombinant mouse or human gamma interferon encapsulated in liposomes
Stable Conformation of an Interferon-γ Receptor Binding Peptide in Aqueous Solution Is Required for Interferon-γ Antagonist Activity
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