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Abstract
Grant Number: 1R43DK064469-01 PI Name: WONG, SO M. PI Email: sow@genetransfer.com PI Title: Project Title: A new hepatocyte-specific ligand for gene delivery Abstract: DESCRIPTION (provided by applicant): We have recently identified a protein, the T7 phage tail fiber protein (p17), which initiated the rapid and selective uptake of the intact T7 phage head, a 60 nm DNA containing icosahedral protein shell, by mouse hepatocytes in vivo. We mapped the hepatocyte-targeting function to the central part of the protein a triple helix forming rod domain. Both the full-length p17 and rod domain alone were able to initiate the accumulation of various protein fusion partners into hepatocytes in vivo. We postulate that this protein will be a powerful new targeting signal for liver gene delivery. The overall goal for this phase I proposal is to determine if the highly efficient p17 mediated hepatocyte targeting of the relatively large T7 phage can be capitalized for hepatocyte specific delivery of heterologous DNA particles. In order to evaluate the potential of pl 7 as a targeting ligand, the first technical hurdle is to develop linkage technology for attaching p17 to DNA particles so that the function of the protein is also preserved. Once a functional attachment method is developed the utility to deliver Virus' proprietary DNA particles systems will be assessed. Successful outcome of this proposal will form basis for further development.
Thesaurus Terms:
bacteriophage T7, gene delivery system, ligand, liver cell, technology /technique development, virus protein
binding protein, biotin, method development
biotechnology, confocal scanning microscopy, flow cytometry, laboratory mouse
Institution: MIRUS CORPORATION 505 S ROSA RD, #104 MADISON, WI 53711 Fiscal Year: 2003 Department: Project Start: 15-JUN-2003 Project End: 31-MAY-2004 ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES IRG: ZRG1
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