Adenoviral vectors gene therapy products

Bauer SR, Pilaro AM, Weiss KD, Testing of adenoviral vector gene transfer products FDA expectations. In Adenoviral Vectors for Gene Therapy. Curiel DT, Douglas JT. eds. San Diego Academic Press, 2002 615-53. 

A. OTC is a metabolic enzyme required to break down ammonia. Total lack of this enzyme leads to death shortly after birth owing to a buildup of ammonia. The partial presence of OTC also leads to accumulation of ammonia, which can be controlled by drugs and dietary intake. The genetic cause of this disease, its morbidity, and the need for rapid production of OTC by adenoviral vectors may extend the life span of OTC-deficient newborns to allow for drug treatment and dietary manipulation. Jesse Gelsinger, the 18-year-old patient who was the first patient to die on a phase I gene therapy trial, had OTC deficiency. 

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). 

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