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- Title
876. Development of Novel Angiogenic DNA Medicine Using a Genomic/cDNA Hybrid of Hepatocyte Growth Factor Gene.
- Authors
Woong Hahn; Dong-Sik Kim; Wook-Bum Pyun; Won-Sun Yoo; Sun-young Kim; Jong-Mook Kim
- Abstract
Background Hepatocyte growth factor (HGF) has angiogenic and antifibrotic activity and two isoforms of HGF are naturally expressed by alternative splicing. Here, we developed genomic/cDNA hybrids of HGF gene, which can generate two isoforms of HGF simultaneously and efficiently. We examined therapeutic potential of this novel form of HGF gene both in rabbit ischemic limb disease model and rat ischemic heart disease model. Methods and results We generated a series of genomic/cDNA hybrids of HGF gene. Comparative analysis on RNA expression pattern and efficiency of these constructs showed that the hybrid called HGF-X7 could express two isoforms of HGF more efficiently than cDNA of HGF and other hybrids. Next we compared the therapeutic potential of HGF-X7 expression DNA VM202 with that of VEGF165 DNA. The number of collateral vessels, capillary density and blood flow were significantly increased in HGF-X7 group in rabbit model as compared with VEGF165 and control group. Furthermore, ejection fraction, viable heart muscle area and capillary density were also considerably increased in HGF-X7 group in rat model. These results provided the first demonstration that the transfer of genomic/cDNA hybrid of HGF gene could be a promising treatment modality in human cardiovascular disease.Molecular Therapy (2006) 13, S337–S337; doi: 10.1016/j.ymthe.2006.08.964
- Subjects
HEPATOCYTE growth factor; RNA; BLOOD flow; CARDIOVASCULAR diseases; GENETIC transformation
- Publication
Molecular Therapy, 2006, Vol 13, pS337
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.964