Adenoviral

Ehrhardt A, Xu H, Dillow AM, Bellinger DA, Nichols TC, Kay MA (2003) A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia. Blood 102 2403-2411... 

Eiedler M, Rodicker E, Salucci V, Lu M, Aurisicchio L, Dahmen U, Jun L, Dirsch O, Putzer BM, Palombo E, Roggendorf M (2004) Helper-dependent adenoviral vector-mediated delivery of woodchuck-specific genes for alpha interferon (IFN-alpha) and IFN-gamma IFN-alpha but not IFN-gamma reduces woodchuck hepatitis virus replication in chronic infection in vivo, J Virol 78 10111-10121... 

Gene therapy for rectification of defects in the enzymes of the urea cycle is an area of active investigation. Encouraging preliminary results have been obtained, for example, in animal models using an adenoviral vector to treat citrullinemia. 

Hsu, C.-P., et al. Overexpression of human intestinal oligopeptide transporter in mammalian cells via adenoviral transduction. Pharm. Res. 

Trepel M, Grifman M, Weitzman MD et al. Molecular adaptors for vascular-targeted adenoviral gene delivery. Hum Gene Ther 2000 11 1971-1981. 

Viral vector manufacture for therapeutic purposes involves initial viral propagation in appropriate animal cell lines, viral recovery, concentration, purification and formulation. A generalized manufacturing scenario for adenoviral-based vectors is outlined in Figure 14.7. The manufacture of alternative viral vectors likely follows a substantially similar approach. 

Figure 14.7 Large-scale manufacture of adenoviral vectors for use for gene-therapy-based clinical protocols. Refer to text for details...

A broadly similar approach to that of Gendicine is being adopted by some Western companies, including Introgen Therapeutics (USA), whose p53 adenoviral-based drug Advexin has entered phase III clinical trials for sqamous cell carcinoma in 2006. 

The possibility of gene therapy for these disorders is a subject of intense scrutiny [38]. An adenoviral vector containing a cDNA for the OTC gene has been given to mice with a congenital deficiency of OTC. The result was... 

Ye, X., Robinson, M. B., Batshaw, M. L., Furth, E. E., Smith, I. and Wilson, J. M. Prolonged metabolic correction in adult ornithine transcarbamylase-deficient mice with adenoviral vectors. / Biol. Chem. 271 3639-3646,1996. 

Fig. 11.1 Localization of adenoviral mediated GFP expression in the mouse myocardium. GFP is targeted to T tubules along myofibers and to nuclei of cardiomyocytes. Red autofluorescence of cardiomyocytes and erythrocytes was captured with a filter exciting the autofluorescence in red spectrum under a longer exposure than with the filter exciting fluorescence in the green spectrum. Nuclei are counterstained with DAPI. Courtesy of Larissa Fabritz...

Hayashi Y (2000) The molecular genetics of recurring chromosome abnormalities in acute myeloid leukemia [In Process Citation]. Semin Hematol 37 368-380 Heery DM, Kalkhoven E, Hoare S, Parker MG (1997) A signature motif in transcriptional co-activators mediates binding to nuclear receptors [see comments]. Nature 387 733-736 Ida K, Kitabayashi I, Taki T, Taniwaki M, Noro K, Yamamoto M, Ohki M, Hayashi Y (1997) Adenoviral E 1 A-associated protein p300 is involved in acute myeloid leukemia with t(ll 22)(q23 ql3). Blood 90 4699-4704... 

Romanczuk H, Galer CE, Zabner J, et al. Modihcation of an adenoviral vector with biologically selected peptides a novel strategy for gene delivery to cells of choice. Hum Gene Ther 1999 10(16) 2615-2626. 

J. Kuball, M. Schnler, E. Antunes-Ferreira, W. Herr, M. Neumann, E. Obenaner-Kntner, E. Westreich, C. Huber, T. Wolfel, and M. Theobald, Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector based vaccination in mice bnt not man. Gene Therapy, 833-843 (2002). 

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