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Generation of Expression Plasmids for Angiostatin, Endostatin and Timp-2 for Cancer Gene Therapy
- Source :
- Scopus-Elsevier
- Publication Year :
- 1999
- Publisher :
- SAGE Publications, 1999.
-
Abstract
- Antiangiogenic therapy may represent a promising approach to cancer treatment. Indeed, the efficacy of endogenous angiogenesis inhibitors, including angiostatin, endostatin and TIMPs, has been demonstrated in many types of solid tumors in animal models. In view of the possible problems associated with long-term administration of inhibitors as recombinant proteins, we propose their delivery as nucleic acids through a gene therapy approach. To this end, eukaryotic expression constructs for murine angiostatin and endostatin as well as human TIMP-2 were generated, and characterized in vitro. All constructs carry the relevant cDNAs under the control of the strong HCMV promoter/enhancer, and cleavable leader signals to allow protein secretion. Expression of the angiogenesis inhibitors was detected by in vitro transcription/translation experiments as well as transfection of 293T cells, followed by Western blotting (WB) or radioimmunoprecipitation analysis of both cell lysates and supernatants (SNs). These constructs might be used for in vivo intramuscular delivery of plasmid DNA and as a set of reagents for the development of retroviral as well as adeno-associated viral (AAV) vectors expressing angiogenesis inhibitors.
- Subjects :
- 0301 basic medicine
Cancer Research
Angiogenesis
Genetic enhancement
Clinical Biochemistry
Angiogenesis Inhibitors
Biology
Transfection
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
Plasmid
Neoplasms
Humans
Enhancer
Angiostatins
Tissue Inhibitor of Metalloproteinase-2
Angiostatin
HEK 293 cells
Plasminogen
Genetic Therapy
Peptide Fragments
Endostatins
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
Collagen
Endostatin
Plasmids
Subjects
Details
- ISSN :
- 17246008
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- The International Journal of Biological Markers
- Accession number :
- edsair.doi.dedup.....6bafa56ceb6b647f869deaa1915847e8