Viral Vectors Selective for Metastatic Breast Cancer Tumor Cells
Abstract
We are developing gene therapy vectors derived from purified polyomavirus capsid proteins and genes assembled into chromatin. We hope to achieve selective targeting of the vectors by expressing on their surface, domains that bind receptors present on the surface of cancer cells. During the past year we have modified the polyomavirus VPl capsid protein to contain sequences derived from urokinase plasminogen activator (uPAr) responsible for binding to the urokinase plasminogen activator receptor (uPAr). Also, as a control, we have modified the VPl protein with the FLAG epitope. The insertions of the uPAr sequences have occurred at surface-exposed loops in the VPl protein, defined by x-ray crystallographic analysis. These modified VPl proteins have been expressed in E.coli and in insect cells. Methods for their purification have been developed, and their capacity to assemble into virion-like particles (VLPs) assessed by electron microscopy. While we have been able to assemble wild type VPl expressed in either E.coli or insect cells into VLPs, only the modified VPls expressed in insect cells form VLPs. This next year we plan to incorporate into them the chromatin-assembled DNAs and to assess their uptake by cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2000
- Accession Number
- ADA388821
Entities
People
- William Folk
Organizations
- University of Missouri