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Combination of optison with ultrasound and electroporation increases albumin and thrompoietin transgene expression whilst elongation factor promoter prolongs its duration

Habib, Nagy and Havlik, Roman and Jiao, Long and Kiri, Arpna and Jensen, Steen and Nicholls, Joanna and Sarraf, Catherine and Goldspink, Geoffrey and Davies, Anthony and Slavik, Ludek and Wood, Chris and Tiraby, Michele and Drocourt, Daniel and Rynes, Jean-Paul and Smadja, Claude and Tiraby, Jean Gerard (2004) Combination of optison with ultrasound and electroporation increases albumin and thrompoietin transgene expression whilst elongation factor promoter prolongs its duration. Gene Therapy and Molecular Biology, 8 (A). pp. 1-8.

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Abstract

Hypoalbuminaemia and thrombocytopaenia are two clinical problems frequently encountered in patients with chronic liver failure or cancer following treatment with chemotherapy. The current study was designed to assess the magnitude and duration of thrombopoietin and albumin transgene expression hoping to increase the production of albumin and platelets. Immunocompetent and immunocompromised (nude) mice were injected intramuscularly with plasmids expressing either human serum albumin or human thrombopoietin. The therapeutic expression cassette of the plasmids was driven by either CMV or elongation factor 1- promoters respectively. In order to achieve muscle specific expression both gene constructs included the myosin light chain enhancer. The experiment was conducted in a group of mice which were injected with the transgene plasmid either in normal saline or plasmid followed by electroporation, ultrasound, optison and a combination of all three to increase transgene expression. The result showed that plasmids with the CMV promoter induced the highest transgenic expression lasting for one week whilst plasmids with the elongation factor 1-alpha promoter produced a weaker expression lasting for a longer and more stable duration of expression up to 3 months in both immunocompetent and nude mice. The combination of electroporation and ultrasound with Optison TM provided the highest transgene expression. We concluded that it would be possible to increase albumin and platelets production by an intramuscular injection of plasmids expressing human albumin and thromopoietin. A combination of electroporation and ultrasound with Optison TM can increase their expression.

Item Type:Article
Uncontrolled Keywords:Gene therapy, liver failure, hypoalbuminaemia, thrombocytopaenia
Research Community:University of Westminster > Life Sciences, School of
ID Code:3228
Deposited On:13 Feb 2007
Last Modified:11 Aug 2010 15:31

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