Renal Diseases as Targets of Gene Therapy

Author(s):  
Brett Phillips ◽  
Nick Giannoukakis ◽  
Massimo Trucco
Keyword(s):  
2015 ◽  
Vol 8 (1) ◽  
pp. 136-147
Author(s):  
John Foreman

The number of genes associated with renal disease is increasing every day and this has led to a clearer understanding of the pathophysiology of renal disease in many disorders. It is also appreciated now that a genetic mutation(s) underlie many renal syndromes. Genetic testing may also offer the possibility to diagnose some renal diseases without the need for a renal biopsy. It also allows the prenatal diagnosis of certain renal diseases in at risk fetuses or identification of potential renal disease before it has become manifest. Finally, identification of a specific gene mutation holds the possibility of correction though gene therapy in the future. It is increasingly clear that many renal disorders in pediatrics are a consequence of genetic mutations. In the future, genetic testing will become as easy and as common as ordering a serum creatinine today.


2004 ◽  
Vol 65 (5) ◽  
pp. 1551-1555 ◽  
Author(s):  
Enyu Imai ◽  
Yoshitsugu Takabatake ◽  
Masayuki Mizui ◽  
Yoshitaka Isaka
Keyword(s):  

1999 ◽  
Vol 10 (9) ◽  
pp. 1908-1915 ◽  
Author(s):  
MICHAEL S. LIPKOWITZ ◽  
BASIL HANSS ◽  
NATALIE TULCHIN ◽  
PATRICIA D. WILSON ◽  
JESSICA C. LANGER ◽  
...  

Abstract. There has been an increasing interest recently in the possibility of treating renal diseases using gene therapy. The ability to pursue gene therapy for renal diseases has been limited by the availability of an adequate system for gene delivery to the kidney. Adeno-associated virus (AAV) is a defective virus of the parvovirus family that has a number of properties attractive for renal gene delivery: recombinant AAV contains no viral genes; expression of genes delivered by these vectors does not activate cell-mediated immunity; the virus is able to transduce nondividing as well as dividing cells; and both wild-type and recombinant AAV integrate into the host chromosome resulting in long-term gene expression. Studies were performed to determine whether AAV can deliver reporter genes to kidney cells in vitro and in vivo. These studies show that AAV can deliver reporter genes with approximately equal efficiency to human mesangial, proximal tubule, thick ascending limb, collecting tubule, and renal cell carcinoma cells in primary culture. Immortalized mouse mesangial cells are transduced at a much greater efficiency. Transduction can be enhanced by pharmaceutical agents up to sevenfold in primary cells (transducing up to 20% of primary cells per well) and as much as 400-fold in immortalized mesangial cells. AAV delivered in vivo by intraparenchymal injection results in at least 3 mo of reporter gene expression in tubular epithelial, but not glomerular or vascular, cells at the injection site. These data indicate that AAV can deliver genes to renal cells both in vitro and in vivo resulting in prolonged gene expression, and thus AAV can be a useful tool for renal gene delivery.


2004 ◽  
Vol 43 (2) ◽  
pp. 85-96 ◽  
Author(s):  
Enyu IMAI ◽  
Yoshitaka ISAKA
Keyword(s):  

Author(s):  
K. Chien ◽  
R.C. Heusser ◽  
M.L. Jones ◽  
R.L. Van de Velde

Silver impregnation techniques have been used for the demonstration of the complex carbohydrates in electron microscopy. However, the silver stains were believed to be technically sensitive and time consumming to perform. Currently, due to the need to more specifically evaluate immune complex for localization in certain renal diseases, a simplified procedure in conjunction with the use of the microwave has been developed and applied to renal and other biopsies. The procedure is as follows:Preparation of silver methenamine solution:1. 15ml graduated, clear polystyrene centrifuge tube (Falcon, No. 2099) was rinsed once with distilled water.2. 3% hexamethylene tetramine (methenamine) was added into the centrifuge tube to the 6ml mark.3. 3% silver nitrate was added slowly to the methenamine to the 7ml mark while agitating. (Solution will instantly turn milky in color and then clear rapidly by mixing. No precipitate should be formed).4. 2% sodium borate was added to the solution to the 8ml mark, mixed and centrifuged before use.


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