Abstract
Publisher Summary This chapter discusses the construction of multidrug resistance gene ( MDR1 ) adeno-associated virus vectors (AAV) for gene therapy. Because of the large size of the MDR1 cDNA, the AAV coding sequences must be deleted prior to the insertion of MDR1 between the inverted terminal repeats (ITRs) of recombinant AAV (rAAV) vectors meant for transduction protocols. Whether all rep negative rAAV vectors are capable of stable integration, the mechanisms that contribute to site-specific integration needs to be investigated. The fact that rAAVs frequently remain episomal and may be diluted and lost with cell division may limit the use of AAV vectors when long-term expression is expected. Selectable markers, such as MDR1 may be possible to maintain nonintegrated episomal rAAV in proliferating cells because only cells carrying such episomal AAV-MDR1 survive the selection.
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