Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Direct transfer of new genetic information to keratinocytes in epidermis may prove effective in treating certain genodermatoses; however, current methods for in vivo gene transfer to skin do not lead to persistence of the transgene. The goal of this study was to explore direct gene transfer using retrovirus-mediated transduction. Retroviral vectors integrate a DNA copy of their genome into the host chromosome and therefore have the potential to effect a permanent gene therapy. To facilitate development of methods for in vivo transduction with retroviral vectors, a porcine skin organ culture model was constructed in which the denuded surface was repopulated with replicating keratinocytes from hair follicles and epidermal remnants. In situ transduction was carried out by topical application of two retrovirus vectors, MFGlacZ (10(7) blue forming units per ml) and LZRN pseudotyped with the G protein of vesicular stomatitis virus (VSV) (10(9) colony forming units per ml), each encoding the beta-galactosidase reporter gene and the latter encoding the neomycin phosphotransferase selectable gene. Beta-galactosidase expressing cells were observed more frequently with LZRN than with MFGlacZ; however, transduction efficiency remained low in both instances. At equivalent titers, the VSV-G pseudotyped retroviral vector was shown to transduce porcine keratinocytes more efficiently than a similar vector with the amphotropic envelope. The number of beta-gal+ cells in organ culture could be increased by selection of LZRN-transduced cells in situ with G418. To achieve transduction of epidermis in vivo, these studies point out the importance of high titer retroviral vectors, pseudotyping with VSV-G protein, and in situ selection.
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PMID:Retrovirus-mediated transduction of porcine keratinocytes in organ culture. 974 Feb 46

We have developed an ex vivo gene transfer technique to rabbit arterial wall using autologous smooth muscle cells (SMCs). SMCs were harvested from rabbit ear artery, transduced in vitro with vesicular stomatitis virus G-glycoprotein pseudotyped retrovirus or feline immunodeficiency virus (FIV) and returned to the adventitial surface of the carotid artery using a periadventitial silicone collar or collagen sheet placed around the artery. Beta-galactosidase (lacZ) and human apolipoprotein E3 (apoE3) cDNAs were used as transgenes. After retrovirus-mediated gene transfer of lacZ the selected cells implanted with high efficiency and expressed lacZ marker gene at a very high level 7 and 14 days after the operation. The level of lacZ expression decreased thereafter but was still detectable 12 weeks after the gene transfer, and was exclusively localized to the site of cell implantation inside the collar. Utilizing FIV vector expressing apoE3, low levels of apoE were measured from serum collected from a low-density lipoprotein receptor deficient Watanabe heritable hyperlipidemic rabbits 1 month after the gene transfer. The physiological effect of apoE expression was detected as transiently elevated serum cholesterol levels. The results indicate that the model can be used for high efficiency local gene transfer in arteries, e.g. during vascular surgery. The model is also valuable for studying expression, stability and safety of new gene transfer vectors and their expression products in vivo.
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PMID:Feline immunodeficiency virus and retrovirus-mediated adventitial ex vivo gene transfer to rabbit carotid artery using autologous vascular smooth muscle cells. 1501 Feb 68