ABSTRACT
In the past decade, there has been increasing interest in the use of oligonucleotides as vectors for gene therapy for two major reasons. First, oligonucleotides have been found to have unique characteristics as drugs to modify the genome or the transcriptome. Investigators have capitalized on these characteristics to use oligonucleotides to alter genomic sequences and to regulate RNA processing. Second, oligonucleotides have distinct advantages over other gene therapy vectors, particularly viral vectors. Hurdles or limitations of virus-mediated gene therapy for Duchenne muscular dystrophy (DMD) (see Chapters 17-19) that are obviated by some or all oligonucleotide vectors include immune responses against viruses themselves and viral-encoded gene products, limitations of viral packaging size for such large cDNAs as dystrophin, non-sustained transgene expression for both non-integrating and integrating viruses, and the risk of insertional
mutagenesis for integrating viral vectors. In addition, the cost of large-scale vector production for human gene therapy, including the cost of quality control, promises to be far less for non-viral vectors such as oligonucleotides than for viral vectors.
