Viral Vectors Selective for Metastatic Breast Cancer Tumor Cells
Abstract
We are developing gene therapy vectors derived from purified polyomavirus capsid proteins. We hope to achieve selective targeting of the vectors by expressing on their surface, sequences that bind receptors present on the surface of cancer cells. We have modified the polyomavirus VP1 capsid protein to contain sequences derived from urokinase plasminogen activator (uPA) responsible for binding to the urokinase plasminogen activator receptor (uPAr) and with sequences capable of binding to the ErbB2 receptor. These modified VP1 proteins have been expressed in insect cells. Methods for their purification have been developed, and their capacity to assemble into virion-like particles (VLPs) assessed by electron microscopy and by sedimentation analyses. We have demonstrated self-assembly of vP1 proteins containing both uPA and ErbB2 ligands into VLPs, which should enhance the specificity of binding to cells expressing both receptors. We have determined that the modified vP1 loses its capacity to bind to sialic acid, a major component of the normal binding of polyomavirus to cells, and we are presently attempting to determine the specificity of the homotypic and heterotypic VLP for cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2001
- Accession Number
- ADA403699
Entities
People
- William Folk
Organizations
- University of Missouri