Sondas de acera

In this work, combinations of regulatory elements were used to optimise the production

of growth hormone in differentiated muscle cells transfected in vitro. However, the

plasmid vector which generated the highest levels o f GH in vitro did not increase the

growth rate of dwarf rats when injected into skeletal muscle in vivo, although this

method was sufficient to increase local IGF-1 levels in the colons of these animals. Although, growth rate might be changed by modifying the method o f plasmid dehvery, there are reasonable safety concerns regarding continuous long term release of GH, and production of IGF-1. Furthermore, repeated administration of plasmids may be detrimental in some individual patients. A number of methods have been used to mimic physiological GH secretion patterns; however, these are only available in viral and cell based gene delivery systems at present. In summary, intramuscular gene transfer of GHRH, GH and IGF-1 may offer some advantages over current methods of therapeutic protein administration, if appropriate levels of protein expression can be generated in

muscle. However, the local and the systemic effects of protein release must be studied further, as must the long term effects of vector administration.

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