title: Shedding of clinical-grade lentiviral vectors is not detected in a gene therapy setting.
abstract: Gene therapy using viral vectors that stably integrate into ex vivo cultured cells holds great promises for the treatment of monogenic diseases as well as cancer. However, carry-over of infectious vector particles has been described to occur upon ex vivo transduction of target cells. This, in turn, may lead to inadvertent spreading of viral particles to off-target cells in vivo, raising concerns for potential adverse effects, such as toxicity of ectopic transgene expression, immunogenicity from in vivo transduced antigen-presenting cells and, possibly, gene transfer to germline cells. Here, we have investigated factors influencing the extent of lentiviral vector (LV) shedding upon ex vivo transduction of human hematopoietic stem and progenitor cells. Our results indicate that, although vector carry-over is detectable when using laboratory-grade vector stocks, the use of clinical-grade vector stocks strongly decreases the extent of inadvertent transduction of secondary targets, likely because of the higher degree of purification. These data provide supportive evidence for the safe use of the LV platform in clinical settings.
authors.affiliation: Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cesani
authors.affiliation: Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Plati
authors.affiliation: 1] Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy [2] Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Lorioli
authors.affiliation: Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Benedicenti
authors.affiliation: Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Redaelli
authors.affiliation: Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Dionisio
authors.affiliation: Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Biasco
authors.affiliation: Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Montini
authors.affiliation: 1] Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy [2] Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Naldini
authors.affiliation: Division of Regenerative Medicine and Stem Cells, San Raffaele Scientific Institute, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Biffi
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism; D017201:Virus Shedding
chemical_list: D018952:Antigens, CD34