New paradigms for gene transfer: RNA trans-splicing and small interfering RNA as therapeutic strategies

If successful, the sustained and regulated expression of therapeutic proteins secreted from a variety of tissues would revolutionize the medical treatment of hematologic diseases. The current paradigm that has dominated the gene therapy field since its inception has been the transfer of complementary DNAs (cDNAs) that encode for therapeutic proteins. The transfer of cDNAs can only correct autosomal recessive and sex-linked disorders. In most cases, cDNAs are constructed that lack their endogenous regulatory elements and therefore lose their intrinsic regulation of gene expression. In this article we will describe the use of RNA species to either suppress unwanted gene activity or to repair defective genes. Examples of RNA inhibition and repair will be discussed.