Gene therapy progress and prospects: recent progress in transgene and RNAi expression cassettes

Abstract

Plasmid expression cassette design must include a thoughtful analysis of potentially every nucleotide comprising a covalently closed circular or end-protected linear DNA. This review will discuss recent studies in unraveling the mechanisms of postdelivery gene silencing, codon optimization and promoter identification. The recent discovery of potent RNA interference (RNAi) mechanisms for sequence-specific gene silencing has also invoked a great deal of interest in development of expression cassettes that can produce double-stranded RNA molecules for RNAi. Expression cassettes based on both RNA polymerase II and polymerase III transcription units that generate double-stranded RNA molecules for RNAi will also be discussed.