title: Modulating the expression of disease genes with RNA-based therapy.
abstract: Conventional gene therapy has focused largely on gene replacement in target cells. However, progress from basic research to the clinic has been slow for reasons relating principally to the challenges of heterologous DNA delivery and regulation in vivo. Alternative approaches targeting RNA have the potential to circumvent some of these difficulties, particularly as the active therapeutic molecules are usually short oligonucleotides and the target gene transcript is under endogenous regulation. RNA-based strategies offer a series of novel therapeutic applications, including altered processing of the target pre-mRNA transcript, reprogramming of genetic defects through mRNA repair, and the targeted silencing of allele- or isoform-specific gene transcripts. This review examines the potential of RNA therapeutics, focusing on antisense oligonucleotide modification of pre-mRNA splicing, methods for pre-mRNA trans-splicing, and the isoform- and allele-specific applications of RNA interference.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom. matthew.wood@dpag.ox.ac.uk
authors.forename: Matthew
authors.initials: M
authors.lastname: Wood
authors.forename: Haifang
authors.initials: H
authors.lastname: Yin
authors.forename: Graham
authors.initials: G
authors.lastname: McClorey
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics*; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000628:therapy*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D012313:RNA / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D012322:RNA Precursors / Q000378:metabolism; D012326:RNA Splicing / Q000502:physiology
chemical_list: D016376:Oligonucleotides, Antisense; D012322:RNA Precursors; D012313:RNA