Abstract
Lentiviral gene transfer vectors have a number of potential advantages over gammaretroviral vectors including more efficient transduction of nondividing cells, a more favorable integration site profile, and the ability to accommodate large transgenes. Here, we present long-term follow-up data of animals that received lentivirus-transduced CD34-enriched cells. Six long-term surviving dogs were available for analysis. Transgene expression was analyzed from at least 12 months to more than 5 years after transplantation in peripheral blood cells and multiple cell lineages. All animals demonstrated long-term stable transgene expression in peripheral blood myeloid, lymphoid, and red blood cells as well as in platelets. Vector integration sites were analyzed by linear amplification-mediated polymerase chain reaction and showed a polyclonal repopulation pattern in all animals. There was no evidence of any development of monoclonality or leukemia in the animals. The stable long-term multilineage transgene expression, together with detection of the same integration site in myeloid and lymphoid cells, strongly suggests the transduction of long-term repopulating stem cells. Our data demonstrate safe and efficient transduction of multilineag...Continue Reading
References
Jan 9, 1998·Baillière's Clinical Haematology·C Stocking, C Baum
Mar 27, 2001·Journal of Virology·D S AnR E Donahue
Apr 19, 2002·The New England Journal of Medicine·Salima Hacein-Bey-AbinaMarina Cavazzana-Calvo
Jun 29, 2002·Science·Alessandro AiutiClaudio Bordignon
Oct 16, 2002·Gene Therapy·P A HornH-P Kiem
Jan 17, 2003·The New England Journal of Medicine·Salima Hacein-Bey-AbinaAlain Fischer
Oct 18, 2003·Science·S Hacein-Bey-AbinaM Cavazzana-Calvo
Jan 24, 2004·Blood·Peter A HornHans-Peter Kiem
Jan 27, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christopher BaumDavid A Williams
Jun 18, 2005·Human Gene Therapy·K E BeaglesH-P Kiem
Jan 5, 2006·Human Gene Therapy·Grant TrobridgeHans-Peter Kiem
Apr 4, 2006·Nature Medicine·Marion G OttManuel Grez
Apr 19, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Brian C BeardGrant D Trobridge
May 24, 2007·Human Gene Therapy·Brian C BeardHans-Peter Kiem
Aug 28, 2007·The Journal of Gene Medicine·Michael L EdelsteinJo Wixon
Sep 18, 2007·Molecular Biotechnology·Adam S Cockrell, Tal Kafri
Sep 25, 2007·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Thomas LoweGeorge Somlo
Nov 1, 2007·Current Gene Therapy·Axel Rethwilm
Dec 1, 2007·Nature Methods·Manfred SchmidtChristof von Kalle
Mar 22, 2008·The Journal of Clinical Investigation·Xiao-Bing ZhangHans-Peter Kiem
Aug 9, 2008·The Journal of Clinical Investigation·Salima Hacein-Bey-AbinaMarina Cavazzana-Calvo
Aug 9, 2008·The Journal of Clinical Investigation·Steven J HoweAdrian J Thrasher
Sep 12, 2008·Gene Therapy·B Moreno-CarranzaM Grez
Mar 19, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Giulietta MaruggiAlessandra Recchia
Jun 18, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Olga S KustikovaChristopher Baum
Citations
Dec 17, 2010·Gene Therapy·S CharrierA Galy
Nov 21, 2013·Nature Communications·Lily M DuDavid A Wilcox
May 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Juan FangDavid A Wilcox
Apr 14, 2010·Human Gene Therapy·Christopher Baum
Aug 1, 2012·Human Gene Therapy·Ofer YanayWilliam R A Osborne
Sep 20, 2012·Experimental Hematology·Kerstin CornilsBoris Fehse
Mar 20, 2014·Blood·Christopher R BurtnerHans-Peter Kiem
Sep 1, 2016·Molecular Therapy. Methods & Clinical Development·Elizabeth M EversonGrant D Trobridge
May 24, 2018·Blood·Chang LiAndré Lieber
Mar 30, 2011·Nature Reviews. Genetics·Luigi Naldini
Nov 4, 2017·Cell Stem Cell·Richard A MorganDonald B Kohn