Physiological effects of human growth hormone produced after hydrodynamic gene transfer of a plasmid vector containing the human ubiquitin promotor

Abstract

Human growth hormone (hGH) deficiency causes retarded growth and abnormalities in body fat distribution and abundance, muscle growth, and bone mineralization. While injection of recombinant hGH may reverse or ameliorate symptoms of deficiency, therapy aiming at in vivo synthesis of hGH is still of considerable clinical interest. Hydrodynamic injection of a simple plasmid vector containing a human ubiquitin promotor and the hGH gene were found to result in high and prolonged expression. Synthesis of hGH was achieved both in NOD/SCID mice and in three different inbred strains of immune competent mice. Although hGH antibodies were produced in immunocompetent mice, physiological effects of the protein were documented by increase in body weight, increased serum levels of insulin-like growth factor I and relative increased weight of the internal organs. Nonviral gene therapy may be regarded as a potential future way of reconstituting hGH expression in deficient individuals.

Differential effects on kidney and liver growth of a non-viral hGH-expression vector in hypophysectomized mice

“…In this procedure high-speed tail vein injection of a large volume of naked plasmid DNA solution can induce expression of genes. Although initial reports have indicated a rapid decline in the expression level within days, new reports indicate that stable levels of gene expression can be achieved following a single injection [3,15,19] or after repeated injections [11,23].…”

“…Recently, hydrodynamic gene transfer, a novel efficient method for delivering and expressing foreign genes in vivo, has been described [11,24,3]. In this procedure high-speed tail vein injection of a large volume of naked plasmid DNA solution can induce expression of genes.…”

Gene transfer vector biodistribution: pivotal safety studies in clinical gene therapy development

“…injection of PEI DNA also showed a wide distribution by both routes at early times. 56 Tissue distribution of naked plasmid DNA was also studied in mice 57,58 and rabbits 57 after i.m. and i.v.…”

Use of Ubp1 protease analog to produce recombinant human growth hormone in

“…It is synthesized and secreted by cells known as somatotrophs in the anterior pituitary. In the lifetime of an individual, the highest quantities of growth hormone are produced during puberty in the anterior lobe or glandular portion of the pituitary [24][25][26][27][28]. hGH is synthesized as a precursor and released into the blood following post-translational modifications.…”