Highly Specific Targeting of the TMPRSS2/ERG Fusion Gene in Prostate Cancer Using Liposomal Nanotechnology
Abstract
The TMPRSS2/ERG fusion gene occurs in 15-80% of prostate cancer (PCa) lesions. It is absolutely specific for PCa cells, since the fusion transcript is only present in these cells. There is heterogeneity in the structure of the 5' end of the mRNA transcripts of the fusion gene. 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. We seek to target the four most common and biologically active alternatively spliced fusion gene transcript isoforms using SiRNAs to obtain maximal biological activity in cancers expressing a specific isoform or a combination of isoforms. We propose to use siRNAs specifically targeting the TMPRSS2/ERG mRNA fusion junctions, which are present only in PCa cells, 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, 2010
- Accession Number
- ADA527560
Entities
People
- Bulent Ozpolat
- Michael M. Ittmann
Organizations
- Baylor College of Medicine