title: Gene therapy: too much splice can spoil the dish.
abstract: The use of integrating vectors for gene therapy - required for stable correction of gene expression - carries the risk of insertional mutagenesis, which can lead to activation of a tumorigenic program. In this issue of the JCI, Moiani et al. and Cesana et al. investigate how viral vectors can induce aberrant splicing, resulting in chimeric cellular-viral transcripts. The finding that this is a general phenomenon is concerning, but some of their results do suggest approaches for the development of safeguards in gene therapy vector design.
authors.affiliation: Frontiers-in-Genetics Program and School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. didier.trono@epfl.ch
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
mesh_terms: D017398:Alternative Splicing; D015894:Genome, Human; D006801:Humans; D016086:Lentivirus / Q000502:physiology*; D016180:Lentivirus Infections / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics*; D059467:Transcriptome; D016662:Virus Integration
chemical_list: D020033:Protein Isoforms