新型诱饵受体药物输送技术的生物工程-猫眼课题宝

新型诱饵受体药物输送技术的生物工程

批准号：

7742393

负责人：

Ka-Wai Hui

金额：

$11.2万

依托单位：

ARMAGEN TECHNOLOGIES, INC.

依托单位国家：

美国

项目类别：

财政年份：

2009

资助国家：

美国

项目状态：

已结题

起止时间：

2009-09-01 至 2010-02-28

来源：

https://reporter.nih.gov/project-details/7742393

关键词：

AGT gene Acute Adult Affinity Affinity Chromatography Animal Testing Anions Applications Grants Binding Biological Assay Biomedical Engineering Bioreactors Blood Blood - brain barrier anatomy Blood capillaries Brain Brain Diseases Brain Injuries COS Cells Carbohydrates Cations Cell Line Cells Chemistry Chimeric Proteins Chinese Hamster Chinese Hamster Ovary Cell Chromatography Clinical Trials Clinical trial protocol document Cloning Complementary DNA DNA DNA Sequence Data Development Dihydrofolate Reductase Dose Drug Delivery Systems Drug Kinetics Drug Receptors Electroporation Engineering Enzyme-Linked Immunosorbent Assay Equipment Equus caballus Etanercept Extracellular Domain FDA approved Filtration Future Gene Amplification Gene Fusion Generations Genes Genetic Genetic Engineering Goals Human Hypoxanthines IgG1 Immunoglobulin G Inflammatory Insulin Insulin Receptor Ischemic Stroke Isoelectric Focusing Lead Light Liquid substance Macaca mulatta Mass Spectrum Analysis Measures Mediating Methods Methotrexate Modeling Molecular Sieve Chromatography Monoclonal Antibodies Neomycin resistance gene Nerve Degeneration Neuroglia Ovary Peripheral Pharmaceutical Preparations Pharmacologic Substance Pharmacology and Toxicology Phase Plasma Plasmids Polyacrylamide Gel Electrophoresis Primates Process Production Protein Binding Proteins RNA Recombinant Fusion Proteins Recombinant Proteins Research Research Contracts Robotics Rodent Running Serum Serum-Free Culture Media Site Small Business Innovation Research Grant Sodium Dodecyl Sulfate Specificity Spinal cord injury Sterility Stroke Structure TNFR-Fc fusion protein Technology Temperature Testing Therapeutic Thymidine Transfection Transgenes Tumor Necrosis Factor Receptor Tumor Necrosis Factor-alpha Tumor Necrosis Factors Western Blotting Work antibiotic G 418 base capillary cell bank cytokine design dimer drug development expression vector extracellular fusion gene good laboratory practice human INSR protein human TNF protein humanized monoclonal antibodies in vivo meetings milligram molecular trojan horse neurotechnology neurotrophic factor new technology novel novel strategies peptide permease pre-clinical public health relevance receptor receptor binding research and development transcytosis vector

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DESCRIPTION (provided by applicant): Decoy receptors are potential new pharmaceuticals to treat brain diseases, such as brain injury, spinal cord injury, stroke, or neurodegeneration. However, decoy receptor drugs are large molecule pharmaceuticals that do not cross the blood-brain barrier (BBB). The present work will produce a novel recombinant fusion protein that is able to both (a) bind a human BBB receptor to trigger transport into the brain, and (b) bind human tumor necrosis factor (TNF)-1, to block cytoxic effects of this inflammatory cytokine. A new approach to the BBB delivery of large molecules such decoy receptors is the molecular Trojan horse technology. A bi-functional fusion protein is produced with genetic engineering, wherein the decoy receptor extracellular domain (ECD) is fused to a BBB molecular Trojan horse. The latter is a genetically engineered monoclonal antibody (MAb) that is able to cross the human BBB by receptor-mediated transcytosis on endogenous BBB peptide transport systems. The present work will produce a novel fusion gene encoding the ECD of the human TNF receptor type II and a genetically engineered MAB molecular Trojan horse, which will allow the production of the corresponding fusion protein, AGT-110. The fusion protein genes will be incorporated in a eukaryotic expression vector followed by permanent transfection of host cells. These phase I SBIR studies will enable production of a permanently transfected host cell line for future manufacturing of AGT-110. PUBLIC HEALTH RELEVANCE: Decoy receptors are potential new pharmaceuticals to treat brain diseases, such as brain injury, spinal cord injury, stroke, or neurodegeneration. However, decoy receptor drugs are large molecule pharmaceuticals that do not cross the blood-brain barrier (BBB). The present work will produce a novel recombinant fusion protein that is able to both (a) bind a human BBB receptor to trigger transport into the brain, and (b) bind human tumor necrosis factor-alpha, to block cytoxic effects of this inflammatory cytokine.

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