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

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. 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.

TitleCombination of optison with ultrasound and electroporation increases albumin and thrompoietin transgene expression whilst elongation factor promoter prolongs its duration
AuthorsHabib, 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.
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.

KeywordsGene therapy, liver failure, hypoalbuminaemia, thrombocytopaenia
JournalGene Therapy and Molecular Biology
Journal citation8 (A), pp. 1-8
YearApr 2004
FileHabib_et_al._2004_final.pdf
Publication dates
PublishedApr 2004

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