Transcriptional Targeting in Cancer Gene Therapy

Robson, Tracy; Hirst, David

doi:10.1155/s1110724303209074

Cited by 113 publications

(105 citation statements)

References 199 publications

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“…1 However, only a few promoter systems incorporating both these elements have been utilized. Most recently Wang et al 39 successfully used a synthetic construct using HREs upstream of the Egr-1 promoter to control expression of HSV-TK in A549 lung adenocarcinoma xenografts.…”

Section: Radiosensitization Using Targeted Inos Gene Therapy Ho Mccarmentioning

confidence: 99%

“…A vast array of therapeutic regimens has been reported where transgenes are driven by a range of tissue or tumour specific, or alternatively, externally inducible promoters to achieve spatial and temporal control of gene expression. 1,2 By far the most widely studied system utilizes radiation-inducible elements from the Early Growth Response (Egr-1) gene. Weichselbaum and co-workers 3,4 have had much success using the CArG elements of the Egr-1 gene, reporting transcriptional control with both radiation and chemotherapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

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p21(WAF1)-mediated transcriptional targeting of inducible nitric oxide synthase gene therapy sensitizes tumours to fractionated radiotherapy

et al. 2006

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Section: Radiosensitization Using Targeted Inos Gene Therapy Ho Mccarmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

p21(WAF1)-mediated transcriptional targeting of inducible nitric oxide synthase gene therapy sensitizes tumours to fractionated radiotherapy

et al. 2006

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“…Previous studies have demonstrated that tissue-or tumor-specific promoters, which are highly expressed in the liver, colon, melanoma, prostate or breast cancer, are capable of directing therapeutic gene expression in the tumor cells. [1][2][3][4][5] However, this approach has limitations as many of these promoters are active only in specific tumor types and some of the tissue-specific promoters can lead to serious side effects due to expression of therapeutic genes in normal cells. 1,6,7 Recently, a family of inhibitor of apoptosis (IAP) proteins has been characterized and their roles in blocking apoptotic pathways and heightening resistance to therapeutic reagents have been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Yang

Cao

et al. 2004

Gene Ther

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Increasing evidence indicates that survivin, an inhibitor of apoptosis protein (IAP), is expressed in human cancer cells but is absent from most normal adult tissues. Here, we examined the feasibility of using a survivin promoter (Sur-P) to direct therapeutic expression of a proapoptotic gene specifically in human tumor cells. First, we demonstrated that this promoter was highly active in human tumor cells but not in normal cells. Second, we found that Sur-P activity was upregulated by hypoxia in tumor cells. Third, to further enhance this promoter's activity under hypoxia, we added a hypoxia-responsive element (HRE) from the vascular endothelial growth factor gene promoter in its 5 0 region, and showed that this combination resulted in a further increase in the level of gene expression in hypoxic tumor cells. Finally, we demonstrated that expression of an autocatalytic reverse caspase-3 gene by this promoter specifically induced apoptotic cell death in human tumor cells but not in normal cells. These findings support the use of promoters Sur-P or chimeric HRE-Sur-P for generating novel vectors for cancer gene therapy.

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“…Since they bind to a specific cell surface receptor, envelope proteins are the primary determinants of the cell specificity or tropism of a retrovirus, though additional tissuespecificity can be garnered through the use of promoter or enhancer elements within the virus genome to direct transgene expression (Robson and Hirst, 2003;Romano, 2004). Pseudotyping, the packaging of vectors with any of a number of heterologous viral envelope proteins rather than the retroviral envelope, can offer the ability to change or extend cell tropism (Cronin et al, 2005).…”

Section: Retroviral Vectorsmentioning

confidence: 99%

Library selection and directed evolution approaches to engineering targeted viral vectors

Jang

Lim

Schaffer

2007

Biotech & Bioengineering

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Gene therapy, to delivery of genetic material to a patient for therapeutic benefit, has significant promise for translating basic knowledge of disease mechanism into biomedical treatments. The clinical development of the field has been slowed, however, by the need for improvements in the properties and capabilities of gene delivery vehicles. Vehicles based on viruses offer the potential for efficient gene delivery, but because viruses did not evolve to serve human therapeutic needs, many of their properties require significant improvement, including their safety, efficiency, and capacity for targeted gene delivery. Since viruses are highly complex biological entities, engineering such properties at the molecular level can be challenging. However, there has been significant progress in developing approaches that mimic the mechanisms by which viruses arose in the first place. In particular, library-based selection, the generation of one diverse genetic library and selection for new properties, and directed evolution, based on the multiple rounds of library generation and selection for iterative improvement of function, have strong potential in engineering novel properties into these complex biomolecular assemblies. This review will discuss progress in the application of peptide display, library selection, and directed evolution technologies toward engineering vectors based on retrovirus, adeno-associated virus, and adenovirus that are capable of targeted delivery to specific cell types. In addition to creating biomedically useful products, these approaches have future potential to yield novel insights into viral structure-function relationships.

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Transcriptional Targeting in Cancer Gene Therapy

Cited by 113 publications

References 199 publications

p21(WAF1)-mediated transcriptional targeting of inducible nitric oxide synthase gene therapy sensitizes tumours to fractionated radiotherapy

p21(WAF1)-mediated transcriptional targeting of inducible nitric oxide synthase gene therapy sensitizes tumours to fractionated radiotherapy

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Library selection and directed evolution approaches to engineering targeted viral vectors

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