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Biotech / Medical : RNAi -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (226)	6/10/2004 6:04:42 PM
From: tuck	Read Replies (1) \| Respond to of 671

This company is involved with getting things to cross the BBB that normally can't. One of their programs involves conjugating an expression plasmid with the silencing strand inside a "nanocontainer" with a compound that is able to mediate its transport across the BBB. >>Clinical Cancer Research Vol. 10, 3667-3677, June 1, 2004 Intravenous RNA Interference Gene Therapy Targeting the Human Epidermal Growth Factor Receptor Prolongs Survival in Intracranial Brain Cancer Yun Zhang1, Yu-feng Zhang1, Joshua Bryant2, Andrew Charles2, Ruben J. Boado1,3 and William M. Pardridge1 Departments of 1 Medicine and 2 Neurology, University of California Los Angeles, Los Angeles, California and 3 Armagen Technologies, Inc., Santa Monica, California ABSTRACT Purpose: The human epidermal growth factor receptor (EGFR) plays an oncogenic role in solid cancer, including brain cancer. The present study was designed to prolong survival in mice with intracranial human brain cancer with the weekly i.v. injection of nonviral gene therapy causing RNA interference (RNAi) of EGFR gene expression. Experimental Design: Human U87 gliomas were implanted in the brain of adult scid mice, and weekly i.v. gene therapy was started at day 5 after implantation of 500,000 cells. An expression plasmid encoding a short hairpin RNA directed at nucleotides 2529–2557 within the human EGFR mRNA was encapsulated in pegylated immunoliposomes. The pegylated immunoliposome was targeted to brain cancer with 2 receptor-specific monoclonal antibodies (MAb), the murine 83–14 MAb to the human insulin receptor and the rat 8D3 MAb to the mouse transferrin receptor. Results: In cultured glioma cells, the delivery of the RNAi expression plasmid resulted in a 95% suppression of EGFR function, based on measurement of thymidine incorporation or intracellular calcium signaling. Weekly i.v. RNAi gene therapy caused reduced tumor expression of immunoreactive EGFR and an 88% increase in survival time of mice with advanced intracranial brain cancer. Conclusions: Weekly i.v. nonviral RNAi gene therapy directed against the human EGFR is a new therapeutic approach to silencing oncogenic genes in solid cancers. This is enabled with a nonviral gene transfer technology that delivers liposome-encapsulated plasmid DNA across cellular barriers with receptor-specific targeting ligands.<< Pretty nifty stuff, apparently avoiding breakdown in the bloodstream, as well as getting large molecules to places they can't normally go. Worth watching, but private, and their website goes into no detail at all of the financial side of their business. armagen.com I believe the company may be NeuroGentech renamed. Cheers, Tuck