Transgene Expression and Gene Correction

Towards Clinical Applications of Transgene Expression and Gene Correction... 

The transduction of neurons of the brain and spinal cord by rAAV has also been remarkably efficient in a number of rodent and non-human primate models (Kaplitt et al., 1994 Peel et al., 1997 During et al., 1998 Klein et al., 1998). Stereotactic injection of rAAV into the substantia nigra or striatum has been used to deliver potentially therapeutic genes in animal models of Parkinson Disease (Kaplitt et al., 1994 During et al., 1998 Klein et al., 1998). These studies have shown efficient transgene expression with functional correction in both rodent and primate models. While the transduction of localized areas of the brain or spinal cord appears to be readily practical, the delivery of rAAV to wider regions of the brain, that may be needed for patients with some metabolic disorders, remains challenging. 

DNA molecules that are delivered to the nucleus could be used in two ways in gene therapy. One is transgene expression (gene replacement or augmentation), and the other is gene correction or repair (see Part I, Chapters 6 and 7 and Part 11, Chapter 8). 

The efficiencies of transgene expression with exogenous genes and of gene correction with exogenous nucleic acids are quite dependent on the types of exogenous nucleic acids used (see Part 1, Chapters 9 and 10). In this section, we focus on the requirements of the nucleic acid molecules for the two gene therapy methods. 

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