Alternative Approaches for the Application of Ribozymes as Gene Therapies for Retroviral Infections

Abstract

Publisher Summary Ribozymes (ribonucleotide enzymes) are RNA molecules derived from these self-splicing introns that function as sequence-specific endoribonucleases. The ability to target ribozymes against specific RNA molecules has led to the development of strategies in which ribozymes are employed to specifically destroy gene transcripts and thereby inhibit gene expression. There are at least five ribozyme motifs that show promise as sequence specific inhibitors of gene expression. The function, structure, and possible applications of these ribozymes vary greatly, and some ribozymes may be better suited for a particular application than others. Although theoretically ribozymes could be used in gene therapy approaches to a number of infectious, oncologic, rheumatic, and cardiovascular diseases, most of the work in this field till date has focused on the use of ribozymes to inhibit replication of human immunodeficiency virus type 1 (HIV-1). In tissue culture, ribozymes have shown promise in gene therapy approaches to the inhibition of HIV-1 replication, but the major limitation of this application of ribozymes is the development of systems to efficiently deliver ribozymes to HIV-1 host cells. The efficacy of ribozymes in the treatment of HIV-1 infection ultimately can be determined in clinical trials in HIV-1-infected individuals. Lastly, ribozymes are capable of more than just cleavage of other RNA molecules.