Self-inactivating retroviral vectors with improved RNA processing

Gene Therapy
J KraunusChristopher Baum

Abstract

Three RNA features have been identified that elevate retroviral transgene expression: an intron in the 5' untranslated region (5'UTR), the absence of aberrant translational start codons and the presence of the post-transcriptional regulatory element (PRE) of the woodchuck hepatitis virus in the 3'UTR. To include such elements into self-inactivating (SIN) vectors with potentially improved safety, we excised the strong retroviral promoter from the U3 region of the 3' long terminal repeat (LTR) and inserted it either downstream or upstream of the retroviral RNA packaging signal (Psi). The latter concept is new and allows the use of an intron in the 5'UTR, taking advantage of retroviral splice sites surrounding Psi. Three LTR and four SIN vectors were compared to address the impact of RNA elements on titer, splice regulation and transgene expression. Although titers of SIN vectors were about 20-fold lower than those of their LTR counterparts, inclusion of the PRE allowed production of more than 10(6) infectious units per ml without further vector optimizations. In comparison with state-of-the-art LTR vectors, the intron-containing SIN vectors showed greatly improved splicing. With regard to transgene expression, the intron-containi...Continue Reading

References

Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M GrezW Ostertag
May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·S F YuE Gilboa
Aug 1, 1996·Human Gene Therapy·T M Kinsella, G P Nolan
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·K J Li, H Garoff
Nov 18, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·A SchambachC Baum
Apr 6, 2001·Results and Problems in Cell Differentiation·H Wodrich, H G Kräusslich
Feb 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alexander PfeiferInder M Verma
Mar 9, 2002·Molecular and Cellular Biology·Ileana PopaThomas J Hope
Apr 19, 2002·The New England Journal of Medicine·Salima Hacein-Bey-AbinaMarina Cavazzana-Calvo
Jun 20, 2002·Journal of Virology·Anne-Kathrin ZaissLung-Ji Chang
Jan 4, 2003·Blood·Christopher BaumChristof von Kalle
May 3, 2003·Nature Reviews. Genetics·Clare E ThomasMark A Kay
Jul 2, 2003·Nature Reviews. Cancer·Donald B KohnJoseph C Glorioso
Aug 9, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Donald B KohnUNKNOWN American Society of Gene Therapy (ASGT)
Aug 12, 2003·Human Gene Therapy·Boris EngelsWolfgang Uckert
Dec 19, 2003·Nucleic Acids Research·Keiko AkagiNeal G Copeland
Dec 25, 2003·Journal of Virology·Marc EgelhoferDorothee von Laer

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Citations

Jan 12, 2013·Current Cardiology Reports·Charbel NaimRoger J Hajjar
May 30, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ali RamezaniRobert G Hawley
Jul 30, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Marita BosticardoFabio Candotti
Oct 22, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jason A MetcalfKatherine P Ponder
Apr 23, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Fabrizia UrbinatiPunam Malik
Jul 1, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Fang ZhangAdrian J Thrasher
Oct 20, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wenqin XuMaribeth V Eiden
Jan 9, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Susannah I ThornhillAdrian J Thrasher
Jul 8, 2008·Médecine sciences : M/S·Hubert de VerneuilFrançois Moreau-Gaudry
Mar 21, 2006·Human Gene Therapy·Christopher BaumBoris Fehse
Jan 19, 2007·Journal of Virology·Jens BohneDaniela Zychlinski
Aug 8, 2013·Journal of Cardiovascular Pharmacology·Armen YerevanianRoger J Hajjar
Jun 7, 2005·Expert Opinion on Biological Therapy·Luisa BarzonGiorgio Palù
Jan 15, 2010·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Donald B Kohn
Sep 13, 2015·Current Opinion in Pharmacology·Benjamin C HoughtonAdrian J Thrasher
Mar 31, 2007·Annals of the New York Academy of Sciences·Zhixiong LiChristopher Baum
Oct 23, 2004·Best Practice & Research. Clinical Haematology·Zhixiong LiChristopher Baum
Sep 19, 2006·Journal of Biotechnology·Sayandip MukherjeeJoseph P Dougherty
Aug 25, 2016·Molecular Genetics and Metabolism Reports·Li OuChester B Whitley
Oct 30, 2016·Cancers·Victor M Bii, Grant D Trobridge
Oct 18, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Axel SchambachChristopher Baum
May 16, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·R SchuchtDagmar Wirth
Apr 25, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christopher BaumMelanie Galla
Sep 1, 2017·Human Gene Therapy·Saskia KohlscheenUte Modlich

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