Tumor-Targeted Silencing of Bcl-2/Bcl-xl by Self-Assembled Sirna-Nanovectors as a Novel Molecular Therapy for Breast Cancer
Abstract
The major goal of this Concept Award project is to explore the anti-Her-2 antibody as targeting ligand to establish the self-assembled nanovectors for targeted siRNA delivery to Her-2(+) breast cancer. Our hypothesis is (1) anti-Her-2 antibody will specifically target nanovectors to Her-2(+) breast cancer and thus efficiently deliver siRNA to the target cells; (2) siRNA-nanovectors will potently silence the Bcl-2/Bcl-xL gene expression induce apoptosis in human breast cancer cells that depend on Bcl-2/Bcl-xL for survival. Since the start of this project we have tested various conditions for the self-assembled nanovectors based on our patented nanotechnology platform. However we have met with technical difficulty using original technique of non-covalent complexing some modification is needed to make Herceptin-nanovectors. Therefore we requested and obtained approval a one-year no cost extension to optimize the conditions for nanovectors. Based on the data obtained in this first year the anti-Her-2-nanovector shows increased transfection efficiency in Her-2(+) breast cancer cells with 2-5-fold increase of reporter gene expression as compared with non-targeted one. We have also designed and validated siRNA/shRNA on Bcl-2 and Bcl-xL that can knockdown target genes expression up to 90%. These data provide us the foundation to accomplish the project in the second year.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2007
- Accession Number
- ADA475323
Entities
People
- Liang Xu
Organizations
- University of Michigan