Adenoviral vector

Finally, in situ transient production of enzymes, if the need arises, will be possible by gene therapy in the future. Promising results have been published using short-induction gene vectors (adenoviral systems) for human PON-1 (Cowan et al., 2001 Bradshaw et al., 2005 Fu et al., 2005 Miyoshi et al., 2007 Guns et al., 2008 Duysen et al., 2011), human AChE (Li et al., 2006), hiunan BChE (Chilukuri et al., 2009 Parikh et al., 2011), mutated human BChE that displays high cocaine esterase (Gao et al., 2013), and human prolidase (Aleti et al., 2013). 

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. 

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...

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. 

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). 

Dai Y, Schwarz EM, Gu D, Zhang WW, Sarvetnick N, Verma IM. Cellular and humoral immune responses to adenoviral vectors containing factor IX gene tolerization of factor IX and vector antigens allows for long-term expression. Proc Natl Acad Sci USA 1995 92 1401-1405. 

---