Gene selection strategy

The heterotypic dimerization significantly expands the repertoire for tissue-specific regulation of transcription activity. The tissue-specific expression of a particular pattern of transcriptional activators can be used to select only certain DNA-binding elements out of a series of similar elements, and thus to specifically induce certain genes. This strategy is extensively used by the receptors for retinoic acid (see chapter 4). 

Since the OTC trial, there has been rapid advancement in vector development with marked improvements in the safety (and efficacy) of new viral delivery systems. There is also a better understanding of the immunological responses to gene therapy vectors. The adverse events in the SCID trial are more recent. They appear to be a likely result of the choice of vector (retrovirus) and the ex vivo selection strategy used to modify the affected stem cells of the SCID patients. The risk benefit ratio for gene therapy treatment of these children is still deemed favorable in light of the fact that without treatment, they would not be alive. 

In a selection strategy based on the substrate 1-phenyl-n-propylamine (PPA) as the sole source of nitrogen in a chemostat, a recombinant Pseudomonas putida strain carrying the R-transaminase gene, a single amino acid change, Y112F, presumably at or near the active site, improved enantioselectivity of the reaction of racemic... 

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