Expression of biologically active human insulin-like growth factor-I following intramuscular injection of a formulated plasmid in rats
| Autor: | Jijun Wang, Russ Mumper, Martha French, Dalal Oubari, Alain Rolland, Hiroaki Nitta, Scott Long, Khursheed Anwer, Hector W. Alila, Jeff Nordstrom, Qingsong Liu, Todd Meyer, Michael E. Coleman |
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| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Genetic Vectors Gene Expression Biology Injections Intramuscular Cell Line Mice Plasmid Internal medicine Gene expression Genetics medicine Animals Humans Insulin-Like Growth Factor I Molecular Biology Growth factor Regeneration (biology) Gene Transfer Techniques Skeletal muscle Biological activity Anatomy Rats Inbred F344 Rats Endocrinology medicine.anatomical_structure Cell culture Molecular Medicine Intramuscular injection Plasmids |
| Zdroj: | Human gene therapy. 8(15) |
| ISSN: | 1043-0342 |
| Popis: | Recent evidence has shown that insulin-like growth factor-I (IGF-I) plays an important role in the development, maintenance, and regeneration of peripheral nerves and skeletal muscle. IGF-I offers the potential to treat neuromuscular diseases in humans. We have developed a nonviral gene therapy method to express and produce localized and sustained therapeutic levels of IGF-I within target muscles by intramuscular injection of formulated plasmids. The purpose of the present study was to demonstrate that intramuscular injection of a plasmid encoding human IGF-I (hIGF-I) and engineered to restrict expression to skeletal muscle produces sustained local concentrations of biologically active hIGF-I. Normal rats received a single intramuscular injection of plasmids formulated as a complex with polyvinylpyrrolidone (PVP). Results show that hIGF-I mRNA and hIGF-I protein were detectable in the injected muscles for the duration of the study (28 days), whereas the hIGF-I protein was not detected in blood. Biological activity of hIGF-I was determined by immunodetection of a nerve-specific growth-associated protein, GAP-43, an indicator of motor neuron sprouting. Placement of human growth hormone (hGH) 3' untranslated region enhanced GAP-43 staining, probably due to improved secretion of hIGF-I. Enhanced immunoreactivity of GAP-43 was observed in muscles injected with the formulated hIGF-I plasmid when compared to controls. These results demonstrate that intramuscular injection of hIGF-I plasmid formulated as a complex with PVP produces a localized and sustained level of biologically active hIGF-I. |
| Databáze: | OpenAIRE |
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