Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiency

Molecular Therapy : the Journal of the American Society of Gene Therapy
Susannah I ThornhillAdrian J Thrasher

Abstract

Gene therapy for X-linked severe combined immunodeficiency (SCID-X1) has proven highly effective for long-term restoration of immunity in human subjects. However, the development of lymphoproliferative complications due to dysregulated proto-oncogene expression has underlined the necessity for developing safer vector systems. To reduce the potential for insertional mutagenesis, we have evaluated the efficacy of self-inactivating (SIN) gammaretroviral vectors in cellular and in vivo models of SCID-X1. Vectors incorporating an internal human elongation factor-1alpha regulatory element were capable of fully restoring the lymphoid differentiation potential of gammac-deficient lineage negative cells. Multilineage lymphoid reconstitution of a murine model was achieved at a similar level to that achieved by a conventional long-terminal repeat (LTR)-regulated vector used in previous clinical trials. Functional proliferative responses to mitogenic stimuli were also restored, and serum immunoglobulin levels were normalized. The reduced mutagenic potential conferred by SIN vector configurations and alternative non-LTR-based regulatory elements, together with proven efficacy in correction of cellular defects provides an important platform ...Continue Reading

References

Nov 1, 1991·Science·R KühnW Müller
Jan 17, 1995·Proceedings of the National Academy of Sciences of the United States of America·J P DiSantoK Rajewsky
Nov 25, 1998·British Journal of Haematology·J P GoldmanA J Thrasher
Feb 18, 1999·The New England Journal of Medicine·R H BuckleyF E Ward
Mar 31, 2000·European Journal of Immunology·H WhiteH B Gaspar
Apr 28, 2000·Science·M Cavazzana-CalvoA Fischer
Nov 18, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·A SchambachC Baum
Apr 19, 2002·The New England Journal of Medicine·Salima Hacein-Bey-AbinaMarina Cavazzana-Calvo
Dec 14, 2002·Immunity·Thomas M Schmitt, Juan Carlos Zúñiga-Pflücker
Jan 17, 2003·The New England Journal of Medicine·Salima Hacein-Bey-AbinaAlain Fischer
Jan 22, 2005·Immunological Reviews·Alain FischerMarina Cavazzana-Calvo
Oct 18, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Axel SchambachChristopher Baum
Aug 3, 2007·The Journal of Clinical Investigation·Annette DeichmannMarina Cavazzana-Calvo
Aug 3, 2007·The Journal of Clinical Investigation·Kerstin SchwarzwaelderChristof von Kalle

❮ Previous
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Citations

Feb 4, 2009·Cancer Immunology, Immunotherapy : CII·Wolfgang Uckert, Ton N M Schumacher
Jun 13, 2008·Nature·Heidi Ledford
Sep 25, 2009·Gene Therapy·W QasimA J Thrasher
Jul 1, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Fang ZhangAdrian J Thrasher
Feb 4, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Derek A Persons, Christopher Baum
Apr 1, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Samantha L GinnIan E Alexander
Oct 20, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wenqin XuMaribeth V Eiden
Dec 3, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christopher Baum
Aug 23, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cecilia N BareseCynthia E Dunbar
Dec 5, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kerstin B KaufmannManuel Grez
Mar 22, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Claudia A Montiel-EquihuaH Bobby Gaspar
Oct 5, 2010·Human Gene Therapy·E AlmarzaA J Thrasher
Mar 16, 2011·Human Gene Therapy·Christopher Baum, Axel Schambach
Mar 23, 2011·Oligonucleotides·R Geoffrey SargentDieter C Gruenert
Jun 10, 2008·Current Opinion in Hematology·Robert SokolicFabio Candotti
Apr 23, 2010·Journal of Virology·Julia D SuerthAxel Schambach
Dec 17, 2009·Hematology·Alessandro Aiuti, Maria Grazia Roncarolo
Jul 3, 2013·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Toru Uchiyama, Masafumi Onodera
Oct 14, 2011·Viruses·Tobias MaetzigAxel Schambach
Nov 16, 2013·Therapeutic Delivery·Manfred Ogris
Feb 4, 2014·International Journal of Hematology·Fabio Candotti
Oct 9, 2014·The New England Journal of Medicine·Salima Hacein-Bey-AbinaAdrian J Thrasher
Feb 10, 2012·Advances in Hematology·Emma NicholsonHans Stauss
Jan 1, 2014·Vaccines·Takehiro UraMasaru Shimada
Oct 29, 2015·Critical Reviews in Biochemistry and Molecular Biology·Erik Serrao, Alan N Engelman
Jan 23, 2016·Human Gene Therapy·Marina CavazzanaSalima Hacein-Bey-Abina
Feb 23, 2010·Experimental Cell Research·Berit Falkowska-HansenMarc Kirschner
Apr 22, 2008·Immunology and Allergy Clinics of North America·Adrian J Thrasher
Sep 13, 2015·Current Opinion in Pharmacology·Benjamin C HoughtonAdrian J Thrasher
Feb 25, 2015·Clinical Genetics·A FischerM Cavazzana
Sep 9, 2008·British Journal of Pharmacology·D BouardF-L Cosset
Nov 1, 2015·Human Molecular Genetics·Johannes C M van der Loo, J Fraser Wright
Jun 6, 2015·British Journal of Haematology·Sujal GhoshH Bobby Gaspar
Apr 11, 2015·Human Gene Therapy·Maria Pia Cicalese, Alessandro Aiuti

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