Highly Specific Targeting of the TMPRSS2/ERG Fusion Gene in Prostate Cancer Using Liposomal Nanotechnology
Abstract
The TMPRSS2/ERG fusion gene is detected in about 50% of prostate cancer (PCa) patients. It is highly specific for PCa and involved in proliferation and invasion of PCa cells. Some prostate cancers express a single mRNA type, while others express multiple isoforms of the fusion gene that arise via alternative splicing of the initial fusion transcript. The goal of the project is to target the four most common and biologically active alternatively spliced fusion gene transcript isoforms using specifcaly designed siRNAs to obtain maximal biological activity in cancers expressing the particular isoform or a combination of isoforms. Although siRNA offers a powerful tool to silence gene expression of drugable and undrugable targets, in vivo delivery of siRNA remains a great challenge. Therefore development of tumor-specific safe and effective nanodelivery systems is the main goal of the studies for clinical applications of siRNA-therapeutics. We propose to use nanoliposomes encapsulating siRNAs specifically targeting the TMPRSS2/ERG mRNA fusion junctions, to minimize off-target effects in normal tissues so toxicity should be minimal. Our results support the efficacy of this approach.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2012
- Accession Number
- ADA562254
Entities
People
- Bulent Ozpolat
- Michael Ittmann
Organizations
- The University of Texas MD Anderson Cancer Center