Lentiviral vector integration profiles differ in rodent postmitotic tissues

Lentiviral vectors with self-inactivating (SIN) long terminal repeats (LTRs) are promising for safe and sustained transgene expression in dividing as well as quiescent cells. As genome organization and transcription substantially differs between actively dividing and postmitotic cells in vivo, we hy...

Full description

Saved in:
Bibliographic Details
Main Authors: Bartholomä, Cynthia C. (Author) , Arens, Anne (Author) , Balaggan, Kamaljit S. (Author) , Yáñez-Muñoz, Rafael J. (Author) , Montini, Eugenio (Author) , Howe, Steven J. (Author) , Paruzynski, Anna (Author) , Korn, Bernhard (Author) , Appelt, Jens-Uwe (Author) , MacNeil, Angus (Author) , Cesana, Daniela (Author) , Abel, Ulrich (Author) , Glimm, Hanno (Author) , Naldini, Luigi (Author) , Ali, Robin R. (Author) , Thrasher, Adrian J. (Author) , Kalle, Christof von (Author) , Schmidt, Manfred (Author)
Format: Article (Journal)
Language:English
Published: 2011
In: Molecular therapy
Year: 2011, Volume: 19, Issue: 4, Pages: 703-710
ISSN:1525-0024
DOI:10.1038/mt.2011.19
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/mt.2011.19
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1525001616304269
Get full text
Author Notes:Cynthia C Bartholomae, Anne Arens, Kamaljit S Balaggan, Rafael J Yáñez-Muñoz, Eugenio Montini, Steven J Howe, Anna Paruzynski, Bernhard Korn, Jens Uwe Appelt, Angus MacNeil, Daniela Cesana, Ulrich Abel, Hanno Glimm, Luigi Naldini, Robin R Ali, Adrian J Thrasher, Christof von Kalle and Manfred Schmidt

MARC

LEADER 00000caa a2200000 c 4500
001 1789975670
003 DE-627
005 20230426075831.0
007 cr uuu---uuuuu
008 220217s2011 xx |||||o 00| ||eng c
024 7 |a 10.1038/mt.2011.19  |2 doi 
035 |a (DE-627)1789975670 
035 |a (DE-599)KXP1789975670 
035 |a (OCoLC)1341441751 
040 |a DE-627  |b ger  |c DE-627  |e rda 
041 |a eng 
084 |a 33  |2 sdnb 
100 1 |a Bartholomä, Cynthia C.  |e VerfasserIn  |0 (DE-588)1036481042  |0 (DE-627)751079243  |0 (DE-576)384489524  |4 aut 
245 1 0 |a Lentiviral vector integration profiles differ in rodent postmitotic tissues  |c Cynthia C Bartholomae, Anne Arens, Kamaljit S Balaggan, Rafael J Yáñez-Muñoz, Eugenio Montini, Steven J Howe, Anna Paruzynski, Bernhard Korn, Jens Uwe Appelt, Angus MacNeil, Daniela Cesana, Ulrich Abel, Hanno Glimm, Luigi Naldini, Robin R Ali, Adrian J Thrasher, Christof von Kalle and Manfred Schmidt 
264 1 |c 2011 
300 |a 8 
336 |a Text  |b txt  |2 rdacontent 
337 |a Computermedien  |b c  |2 rdamedia 
338 |a Online-Ressource  |b cr  |2 rdacarrier 
500 |a First published online: 14 December 2016 
500 |a Gesehen am 17.02.2022 
520 |a Lentiviral vectors with self-inactivating (SIN) long terminal repeats (LTRs) are promising for safe and sustained transgene expression in dividing as well as quiescent cells. As genome organization and transcription substantially differs between actively dividing and postmitotic cells in vivo, we hypothesized that genomic vector integration preferences might be distinct between these biological states. We performed integration site (IS) analyses on mouse dividing cells (fibroblasts and hematopoietic progenitor cells (HPCs)) transduced ex vivo and postmitotic cells (eye and brain) transduced in vivo. As expected, integration in dividing cells occurred preferably into gene coding regions. In contrast, postmitotic cells showed a close to random frequency of integration into genes and gene spare long interspersed nuclear elements (LINE). Our studies on the potential mechanisms responsible for the detected differences of lentiviral integration suggest that the lowered expression level of Psip1 reduce the integration frequency in vivo into gene coding regions in postmitotic cells. The motif TGGAA might represent one of the factors for preferred lentiviral integration into mouse and rat Satellite DNA. These observations are highly relevant for the correct assessment of preclinical biosafety studies, indicating that lentiviral vectors are well suited for safe and effective clinical gene transfer into postmitotic tissues. 
700 1 |a Arens, Anne  |d 1980-  |e VerfasserIn  |0 (DE-588)1030235244  |0 (DE-627)734950039  |0 (DE-576)378039490  |4 aut 
700 1 |a Balaggan, Kamaljit S.  |e VerfasserIn  |4 aut 
700 1 |a Yáñez-Muñoz, Rafael J.  |e VerfasserIn  |4 aut 
700 1 |a Montini, Eugenio  |e VerfasserIn  |4 aut 
700 1 |a Howe, Steven J.  |e VerfasserIn  |4 aut 
700 1 |a Paruzynski, Anna  |e VerfasserIn  |0 (DE-588)142778648  |0 (DE-627)640120822  |0 (DE-576)333342526  |4 aut 
700 1 |a Korn, Bernhard  |e VerfasserIn  |0 (DE-588)1163822922  |0 (DE-627)1028164270  |0 (DE-576)508230853  |4 aut 
700 1 |a Appelt, Jens-Uwe  |d 1978-  |e VerfasserIn  |0 (DE-588)1013120035  |0 (DE-627)663353564  |0 (DE-576)346002117  |4 aut 
700 1 |a MacNeil, Angus  |e VerfasserIn  |4 aut 
700 1 |a Cesana, Daniela  |e VerfasserIn  |4 aut 
700 1 |a Abel, Ulrich  |d 1952-  |e VerfasserIn  |0 (DE-588)14287552X  |0 (DE-627)640555403  |0 (DE-576)333774582  |4 aut 
700 1 |a Glimm, Hanno  |d 1967-  |e VerfasserIn  |0 (DE-588)113880677  |0 (DE-627)51985120X  |0 (DE-576)289777879  |4 aut 
700 1 |a Naldini, Luigi  |e VerfasserIn  |4 aut 
700 1 |a Ali, Robin R.  |e VerfasserIn  |4 aut 
700 1 |a Thrasher, Adrian J.  |e VerfasserIn  |4 aut 
700 1 |a Kalle, Christof von  |d 1962-  |e VerfasserIn  |0 (DE-588)1036481115  |0 (DE-627)75107926X  |0 (DE-576)168957396  |4 aut 
700 1 |a Schmidt, Manfred  |d 1967-2022  |e VerfasserIn  |0 (DE-588)122922301  |0 (DE-627)706092430  |0 (DE-576)293477620  |4 aut 
773 0 8 |i Enthalten in  |t Molecular therapy  |d Amsterdam : Elsevier, 2000  |g 19(2011), 4 vom: Apr., Seite 703-710  |h Online-Ressource  |w (DE-627)320415198  |w (DE-600)2001818-6  |w (DE-576)104344695  |x 1525-0024  |7 nnas  |a Lentiviral vector integration profiles differ in rodent postmitotic tissues 
773 1 8 |g volume:19  |g year:2011  |g number:4  |g month:04  |g pages:703-710  |g extent:8  |a Lentiviral vector integration profiles differ in rodent postmitotic tissues 
776 0 8 |i Erscheint auch als  |n Druck-Ausgabe  |a Bartholomä, Cynthia C.  |t Lentiviral vector integration profiles differ in rodent postmitotic tissues  |d 2011  |w (DE-627)1632289008  |w (DE-576)384506208 
856 4 0 |u https://doi.org/10.1038/mt.2011.19  |x Verlag  |x Resolving-System  |z lizenzpflichtig  |3 Volltext 
856 4 0 |u https://www.sciencedirect.com/science/article/pii/S1525001616304269  |x Verlag  |z lizenzpflichtig  |3 Volltext 
951 |a AR 
992 |a 20220217 
993 |a Article 
994 |a 2011 
998 |g 122922301  |a Schmidt, Manfred  |m 122922301:Schmidt, Manfred  |d 140000  |e 140000PS122922301  |k 0/140000/  |p 18  |y j 
998 |g 1036481115  |a Kalle, Christof von  |m 1036481115:Kalle, Christof von  |d 910000  |e 910000PK1036481115  |k 0/910000/  |p 17 
998 |g 113880677  |a Glimm, Hanno  |m 113880677:Glimm, Hanno  |d 910000  |e 910000PG113880677  |k 0/910000/  |p 13 
998 |g 14287552X  |a Abel, Ulrich  |m 14287552X:Abel, Ulrich  |d 910000  |d 999701  |d 50000  |e 910000PA14287552X  |e 999701PA14287552X  |e 50000PA14287552X  |k 0/910000/  |k 1/910000/999701/  |k 0/50000/  |p 12 
998 |g 1013120035  |a Appelt, Jens-Uwe  |m 1013120035:Appelt, Jens-Uwe  |d 50000  |e 50000PA1013120035  |k 0/50000/  |p 9 
998 |g 1163822922  |a Korn, Bernhard  |m 1163822922:Korn, Bernhard  |d 50000  |e 50000PK1163822922  |k 0/50000/  |p 8 
998 |g 142778648  |a Paruzynski, Anna  |m 142778648:Paruzynski, Anna  |d 140000  |e 140000PP142778648  |k 0/140000/  |p 7 
998 |g 1030235244  |a Arens, Anne  |m 1030235244:Arens, Anne  |p 2 
998 |g 1036481042  |a Bartholomä, Cynthia C.  |m 1036481042:Bartholomä, Cynthia C.  |d 50000  |e 50000PB1036481042  |k 0/50000/  |p 1  |x j 
999 |a KXP-PPN1789975670  |e 4061104748 
BIB |a Y 
SER |a journal 
JSO |a {"origin":[{"dateIssuedDisp":"2011","dateIssuedKey":"2011"}],"id":{"eki":["1789975670"],"doi":["10.1038/mt.2011.19"]},"recId":"1789975670","name":{"displayForm":["Cynthia C Bartholomae, Anne Arens, Kamaljit S Balaggan, Rafael J Yáñez-Muñoz, Eugenio Montini, Steven J Howe, Anna Paruzynski, Bernhard Korn, Jens Uwe Appelt, Angus MacNeil, Daniela Cesana, Ulrich Abel, Hanno Glimm, Luigi Naldini, Robin R Ali, Adrian J Thrasher, Christof von Kalle and Manfred Schmidt"]},"title":[{"title":"Lentiviral vector integration profiles differ in rodent postmitotic tissues","title_sort":"Lentiviral vector integration profiles differ in rodent postmitotic tissues"}],"person":[{"family":"Bartholomä","role":"aut","given":"Cynthia C.","display":"Bartholomä, Cynthia C."},{"display":"Arens, Anne","family":"Arens","given":"Anne","role":"aut"},{"family":"Balaggan","given":"Kamaljit S.","role":"aut","display":"Balaggan, Kamaljit S."},{"display":"Yáñez-Muñoz, Rafael J.","role":"aut","given":"Rafael J.","family":"Yáñez-Muñoz"},{"given":"Eugenio","role":"aut","family":"Montini","display":"Montini, Eugenio"},{"display":"Howe, Steven J.","role":"aut","given":"Steven J.","family":"Howe"},{"family":"Paruzynski","role":"aut","given":"Anna","display":"Paruzynski, Anna"},{"given":"Bernhard","role":"aut","family":"Korn","display":"Korn, Bernhard"},{"display":"Appelt, Jens-Uwe","family":"Appelt","given":"Jens-Uwe","role":"aut"},{"role":"aut","given":"Angus","family":"MacNeil","display":"MacNeil, Angus"},{"display":"Cesana, Daniela","given":"Daniela","role":"aut","family":"Cesana"},{"display":"Abel, Ulrich","family":"Abel","role":"aut","given":"Ulrich"},{"display":"Glimm, Hanno","family":"Glimm","given":"Hanno","role":"aut"},{"family":"Naldini","given":"Luigi","role":"aut","display":"Naldini, Luigi"},{"display":"Ali, Robin R.","given":"Robin R.","role":"aut","family":"Ali"},{"display":"Thrasher, Adrian J.","family":"Thrasher","role":"aut","given":"Adrian J."},{"given":"Christof von","role":"aut","family":"Kalle","display":"Kalle, Christof von"},{"family":"Schmidt","given":"Manfred","role":"aut","display":"Schmidt, Manfred"}],"physDesc":[{"extent":"8 S."}],"language":["eng"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"relHost":[{"part":{"text":"19(2011), 4 vom: Apr., Seite 703-710","extent":"8","volume":"19","pages":"703-710","year":"2011","issue":"4"},"id":{"eki":["320415198"],"zdb":["2001818-6"],"issn":["1525-0024"]},"origin":[{"publisher":"Elsevier ; Nature Publ. Group ; Acad. Press","dateIssuedKey":"2000","dateIssuedDisp":"2000-","publisherPlace":"Amsterdam ; New York, NY ; Orlando, Fla."}],"disp":"Lentiviral vector integration profiles differ in rodent postmitotic tissuesMolecular therapy","recId":"320415198","title":[{"subtitle":"official journal of the American Society of Gene Therapy","title":"Molecular therapy","title_sort":"Molecular therapy"}],"pubHistory":["1.2000 -"],"physDesc":[{"extent":"Online-Ressource"}],"language":["eng"],"corporate":[{"role":"isb","display":"American Society of Gene Therapy"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"note":["Gesehen am 28.05.2020"]}],"note":["First published online: 14 December 2016","Gesehen am 17.02.2022"]} 
SRT |a BARTHOLOMALENTIVIRAL2011