The possibilities for non-viral GH gene therapy are studied in immunocompetent dwarf mice (lit/lit). As expression
vector we used a plasmid previously employed in immunodeficient dwarf mice (pUBI-hGH-gDNA) by replacing
the human GH gene with the genomic sequence of mouse-GH DNA (pUBI-mGH-gDNA). HEK-293 human cells transfected
with pUBI-mGH-gDNA produced 3.0 µg mGH/106 cells/day compared to 3.7 µg hGH/106 cells/day for pUBIhGH-
gDNA transfected cells. The weight of lit/lit mice treated with the same two plasmids (50 µg DNA/mouse) by electrotransfer
into the quadriceps muscle was followed for 3 months. The weight increase up to 15 days for mGH, hGH and
saline treated mice were 0.130, 0.112 and 0.027 g/mouse/day. Most sera from hGH-treated mice contained anti-hGH antibodies
already on day 15, with the highest titers on day 45, while no significant anti-mGH antibodies were observed in
mGH-treated mice. At the end of 3 months, the weight increase for mGH-treated mice was 34.3%, while the nose-to-tail
and femur lengths increased 9.5% and 24.3%. Mouse-GH and hGH circulating levels were 4-5 ng/mL 15 days after treatment,
versus control levels of ~0.7 ng GH/mL (P<0.001). In mGH-treated mice, mIGF-I determined on days 15, 45 and
94 were 1.5- to 3-fold higher than the control and 1.2- to 1.6-fold higher than hGH-treated mice. The described homologous
model represents an important progress forming the basis for preclinical testing of non-viral gene therapy for GH deficiency.
Keywords: Gene therapy, homologous model, IGF-I, little mice, mouse growth hormone, non-viral gene transfer.
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