Perspectives for Gene Therapy in Renal Diseases

Renal Pathophysiology After Systemic Administration of Recombinant Adenovirus: Changes in Renal Cytochromes P450 Based on Vector Dose

“…Limited amounts of adenovirus and subsequent transgene expression have been reported in the kidney after intravenous administration of virus (Gonin and Gaillard, 2004;Imai and Isaka, 2004;Ni et al, 2005). Expression of the ␤-galactosidase transgene and the adenovirus itself are also capable of inducing an immune response (Bessis et al, 2004).…”

“…Its role as a life-sustaining organ makes it a prime target for gene therapy of both renal and systemic disorders (Imai and Isaka, 2004;van der Wouden et al, 2004;Worgall, 2005). It also renders the kidney highly susceptible to adverse effects associated with this form of therapy, limiting progress of renal gene transfer in the clinic.…”

“…To date, recombinant adenovirus is considered to be an appropriate vector for in vivo gene transfer to complex organs such as the kidney because it can produce a high level of transgene expression in numerous cell types in a dividing or nondividing state (van der Wouden et al, 2004). Despite this, preclinical studies have described localized, invasive, and somewhat complicated methods to deliver adenoviral vectors to the kidney because of the strong affinity of the virus for the liver and limited levels of renal transgene expression after systemic administration (Gonin and Gaillard, 2004;Imai and Isaka, 2004;Ni et al, 2005). They have also revealed that gene expression patterns are significantly influenced by the manner in which the virus is administered and that these techniques significantly reduce the toxicity and immune response associated with systemic administration of the virus (Imai and Isaka, 2004;van der Wouden et al, 2004).…”

In vivo synthesis and secretion of erythropoietin by genetically modified primary human keratinocytes grafted onto immunocompromised mice

“…For clinical use, recombinant EPO is given to patients with anaemia because of renal insufficiency or suffering from chronic inflammatory diseases or HIV‐infection (6–8). As these patients need long‐term treatment with EPO – a cost‐ and labour‐intensive therapy implying regularly injections of a recombinant hormone with a short half‐life – systemic replacement of EPO by genetically modified cells constitutes an attractive alternative (9,10).…”

The skin as a biofactory for systemic secretion of erythropoietin: potential of genetically modified keratinocytes and fibroblasts

“…However, as these patients need long‐term treatment with EPO, it constitutes a cost and labour‐intensive therapy implying regularly injections of a recombinant hormone with a short half‐life. Thus, systemic replacement of EPO by genetically modified cells constitutes an attractive alternative (13,14). A further advantage is, that production of EPO could be controlled by linking the transferred EPO gene to an inducible promoter activated either by a topically applied drug (15) or even naturally by decreased oxygen pressure stimulating a hypoxia‐response element (16,17).…”