title: Is it going to be SIN?: a European Society of Gene Therapy commentary. Phasing-out the clinical use of non self-inactivating murine leukemia virus vectors: initiative on hold.
abstract: Insertional mutagenesis resulting in a leukaemia-like lymphoproliferative disease, as observed in the X-SCID (severe combined immunodeficiency) clinical trial using a gamma-retroviral vector that transferred a functional copy of the defective gene into hematopoietic precursor cells of affected children, sparked a debate about a ban on conventional gamma-retroviral vectors. This commentary summarizes the relevant data on this topic and concludes that there is no preclinical or clinical evidence as yet that SIN vectors, which self-inactivate the retroviral long terminal repeats (LTRs), will indeed show an improved safety profile. Conventional murine leukaemia virus (MLV) vectors can thus be used further in clinical gene therapy trials but require a thorough case-by-case risk-benefit analysis.
authors.affiliation: Paul-Ehrlich-Institut, Division of Medical Biotechnology, 63225 Langen, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Buchholz
authors.forename: Klaus
authors.initials: K
authors.lastname: Cichutek
mesh_terms: D002648:Child; D002986:Clinical Trials as Topic; D000075202:Contraindications; D005060:Europe; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000009:adverse effects*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D012449:Safety; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D012955:Societies, Medical; D014161:Transduction, Genetic / Q000379:methods*