|Title||Combination of optison with ultrasound and electroporation increases albumin and thrompoietin transgene expression whilst elongation factor promoter prolongs its duration|
|Authors||Habib, N., Havlik, R., Jiao, L., Kiri, A., Jensen, S., Nicholls, J., Sarraf, C., Goldspink, G., Davies, A., Slavik, L., Wood, C., Tiraby, M., Drocourt, D., Rynes, J.P., Smadja, C. and Tiraby, J.G.|
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.
|Keywords||Gene therapy, liver failure, hypoalbuminaemia, thrombocytopaenia|
|Journal||Gene Therapy and Molecular Biology|
|Journal citation||8 (A), pp. 1-8|