Abstract
Deregulated transcriptional machinery is frequently observed in cancer cells, resulting in increased transcription activity and gene expression. In gene therapeutic applications it is feasible to exploit the increased transcriptional activity by using promoters and/or enhancers from highly expressed genes to drive transgene expression. This approach, also known as tissue- or tumor-specific targeting, has been widely used to limit therapeutic gene expression only in cancer cells, allowing systemic administration that targets not only primary but also metastatic tumors. However, most of the cancer-specific promoter activities are weak compared with more potent nonspecific promoters such as cytomegalovirus (CMV) or Rous sarcoma virus. We briefly summarize the uses of cancer-specific or cancer-targeting promoters to increase specificity and expression in select cancer types. In addition, we describe the design of an expression vector that has been successfully used to target multiple cancer types in animal models by amplifying the activities of the specific promoters to levels comparable to the nonspecific CMV promoter and limiting expression in normal cells.
Original language | English (US) |
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Title of host publication | Cancer Gene Therapy by Viral and Non-viral Vectors |
Publisher | Wiley-Blackwell |
Pages | 79-96 |
Number of pages | 18 |
ISBN (Electronic) | 9781118501665 |
ISBN (Print) | 9781118501627 |
DOIs | |
State | Published - Mar 17 2014 |
Keywords
- Breast cancer
- Liver cancer
- Lung cancer
- Pancreatic cancer
- Prostate cancer
- Two-step transcriptional amplification (TSTA)
- VISA
ASJC Scopus subject areas
- General Medicine