By A. Benigni, G. Remuzzi, C. Ronco
At first conceived as a technique to treatment inherited genetic issues, gene remedy has been effectively utilized within the final decade to ameliorate the renal functionality compromised by means of revolutionary renal ailments and to avoid kidney allograft rejection in experimental animals. within the current publication, world-renowned specialists are proposing new insights into viral and non-viral platforms used to impression gene supply, one bankruptcy being devoted to the hot box of RNA interference (RNAi). This latter approach might be effectively utilized in renal ischemia-reperfusion damage, trauma and transplantation. within the close to destiny, gene remedy may additionally end up to be a brand new technique to aim molecules considering tissue harm and irritation procedures that underlie ARF. to date, gene move has been effectively utilized in experimental glomerulonephritis and interstitial fibrosis, and reports in better animals are keenly awaited. additionally lined are concerns regarding transplantation, that's the remedy of selection in lots of end-stage organ mess ups. move of genes whose protein items have immunomodulatory houses have confirmed worthy in treating acute and protracted graft rejection, one of many difficulties now not satisfactorily solved through present anti-rejection medicines. Gene remedy therefore may perhaps develop into a fact in scientific transplantation as soon as its efficacy in greater animals has been verified. final yet no longer least, a potential good thing about specific gene remedy in renal melanoma or HIV-associated nephropathy is explored. protecting a large spectrum of subject matters, this book offers a useful review of present advancements and matters.
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Extra resources for Gene Therapy for Renal Diseases and Transplantation
Example text
TGF- signaling increases mesangial cell proliferation and induces ECM protein synthesis that thickens the BM and causes renal injury, fibrosis and finally renal failure. Inflammatory lymphocyte infiltration can be inhibited by the cytokine IL-10 expression. IL-10 is an inhibitor of proinflammatory cytokine production by Th1 cells and antigen presentation by dentritic cells and macrophages. Choi et al. [49] administered an adenovirus transducing IL-10 by parenchyma injection to a kidney of a focal segmental glomerulosclerosis mouse model.
Similarly, the brain cell population illustrates that the cell populations in the kidney may be differentially bound and infected by different envelopes. A second transduction strategy is to increase the volume and length of time that the viral vector is administered to and resident in the kidney. The renal basement membrane (BM) is the primary barrier that makes gene transfer to certain cell types challenging. The BM is a specialized extracellular MA that anchors endothelial and epithelial cells and surrounds components of the glomeruli, nephron and collecting duct.
The transfection activities of R8-MEND were as high as those of the adenovirus at 1 ϫ 105 particles/cell. As judged from the protein content of the cell lysate after transfection, the R8-MEND showed no significant cytotoxicity, while higher doses of the adenovirus produced significant cytotoxicity (ϳ50% loss of protein content). Amiloride significantly inhibited transfection activity of the R8MEND (reduced by ϳ95%), indicating that macropinocytosis is the major route of efficient gene transfection using R8-MEND [35].