Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk
Lentiviral vectors are attractive tools for liver-directed gene therapy because of their capacity for stable gene expression and the lack of preexisting immunity in most human subjects. However, the use of integrating vectors may raise some concerns about the potential risk of insertional mutagenesi...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
11 February 2011
|
| In: |
Hepatology
Year: 2011, Jahrgang: 53, Heft: 5, Pages: 1696-1707 |
| ISSN: | 1527-3350 |
| DOI: | 10.1002/hep.24230 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/hep.24230 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/hep.24230 
|
| Verfasserangaben: | Janka Mátrai, Alessio Cantore, Cynthia C. Bartholomae, Andrea Annoni, Wei Wang, Abel Acosta-Sanchez, Ermira Samara-Kuko, Liesbeth De Waele, Ling Ma, Pietro Genovese, Martina Damo, Anne Arens, Kevin Goudy, Timothy C. Nichols, Christof von Kalle, Marinee K.L. Chuah, Maria Grazia Roncarolo, Manfred Schmidt, Thierry VandenDriessche, and Luigi Naldini |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1814187103 | ||
| 003 | DE-627 | ||
| 005 | 20230710122557.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220811s2011 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/hep.24230 |2 doi | |
| 035 | |a (DE-627)1814187103 | ||
| 035 | |a (DE-599)KXP1814187103 | ||
| 035 | |a (OCoLC)1389793363 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Mátrai, Janka |e VerfasserIn |0 (DE-588)1265141975 |0 (DE-627)1814187758 |4 aut | |
| 245 | 1 | 0 | |a Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk |c Janka Mátrai, Alessio Cantore, Cynthia C. Bartholomae, Andrea Annoni, Wei Wang, Abel Acosta-Sanchez, Ermira Samara-Kuko, Liesbeth De Waele, Ling Ma, Pietro Genovese, Martina Damo, Anne Arens, Kevin Goudy, Timothy C. Nichols, Christof von Kalle, Marinee K.L. Chuah, Maria Grazia Roncarolo, Manfred Schmidt, Thierry VandenDriessche, and Luigi Naldini |
| 264 | 1 | |c 11 February 2011 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 11.08.2022 | ||
| 520 | |a Lentiviral vectors are attractive tools for liver-directed gene therapy because of their capacity for stable gene expression and the lack of preexisting immunity in most human subjects. However, the use of integrating vectors may raise some concerns about the potential risk of insertional mutagenesis. Here we investigated liver gene transfer by integrase-defective lentiviral vectors (IDLVs) containing an inactivating mutation in the integrase (D64V). Hepatocyte-targeted expression using IDLVs resulted in the sustained and robust induction of immune tolerance to both intracellular and secreted proteins, despite the reduced transgene expression levels in comparison with their integrase-competent vector counterparts. IDLV-mediated and hepatocyte-targeted coagulation factor IX (FIX) expression prevented the induction of neutralizing antibodies to FIX even after antigen rechallenge in hemophilia B mice and accounted for relatively prolonged therapeutic FIX expression levels. Upon the delivery of intracellular model antigens, hepatocyte-targeted IDLVs induced transgene-specific regulatory T cells that contributed to the observed immune tolerance. Deep sequencing of IDLV-transduced livers showed only rare genomic integrations that had no preference for gene coding regions and occurred mostly by a mechanism inconsistent with residual integrase activity. Conclusion: IDLVs provide an attractive platform for the tolerogenic expression of intracellular or secreted proteins in the liver with a substantially reduced risk of insertional mutagenesis. | ||
| 700 | 1 | |a Cantore, Alessio |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bartholomae, Cynthia C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Annoni, Andrea |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wang, Wei |e VerfasserIn |0 (DE-588)125557853X |0 (DE-627)1799704831 |4 aut | |
| 700 | 1 | |a Acosta-Sanchez, Abel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Samara-Kuko, Ermira |e VerfasserIn |4 aut | |
| 700 | 1 | |a De Waele, Liesbeth |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ma, Ling |e VerfasserIn |4 aut | |
| 700 | 1 | |a Genovese, Pietro |e VerfasserIn |4 aut | |
| 700 | 1 | |a Damo, Martina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Arens, Anne |e VerfasserIn |4 aut | |
| 700 | 1 | |a Goudy, Kevin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nichols, Timothy C. |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 L. Chuah, Marinee K. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Roncarolo, Maria Grazia |e VerfasserIn |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 | |
| 700 | 1 | |a VandenDriessche, Thierry |e VerfasserIn |4 aut | |
| 700 | 1 | |a Naldini, Luigi |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Hepatology |d [Alphen aan den Rijn] : Wolters Kluwer Health, 1981 |g 53(2011), 5, Seite 1696-1707 |h Online-Ressource |w (DE-627)268132003 |w (DE-600)1472120-X |w (DE-576)077450183 |x 1527-3350 |7 nnas |a Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk |
| 773 | 1 | 8 | |g volume:53 |g year:2011 |g number:5 |g pages:1696-1707 |g extent:12 |a Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk |
| 856 | 4 | 0 | |u https://doi.org/10.1002/hep.24230 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1002/hep.24230 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20220811 | ||
| 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 | ||
| 998 | |g 1036481115 |a Kalle, Christof von |m 1036481115:Kalle, Christof von |d 910000 |d 50000 |e 910000PK1036481115 |e 50000PK1036481115 |k 0/910000/ |k 0/50000/ |p 15 | ||
| 998 | |g 125557853X |a Wang, Wei |m 125557853X:Wang, Wei |d 50000 |e 50000PW125557853X |k 0/50000/ |p 5 | ||
| 999 | |a KXP-PPN1814187103 |e 417855915X | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"relHost":[{"origin":[{"dateIssuedKey":"1981","publisherPlace":"[Alphen aan den Rijn] ; Philadelphia, Pa. ; New York [u.a.]","publisher":"Wolters Kluwer Health ; Saunders ; Wiley Interscience","dateIssuedDisp":"1981-"}],"title":[{"title":"Hepatology","title_sort":"Hepatology","subtitle":"official journal of the American Association for the Study of Liver Diseases"}],"physDesc":[{"extent":"Online-Ressource"}],"part":{"extent":"12","issue":"5","text":"53(2011), 5, Seite 1696-1707","volume":"53","year":"2011","pages":"1696-1707"},"id":{"zdb":["1472120-X"],"doi":["10.1002/(ISSN)1527-3350"],"issn":["1527-3350"],"eki":["268132003"]},"note":["Gesehen am 28.02.08"],"disp":"Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic riskHepatology","recId":"268132003","language":["eng"],"type":{"bibl":"periodical","media":"Online-Ressource"},"pubHistory":["1.1981 -"]}],"note":["Gesehen am 11.08.2022"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"id":{"doi":["10.1002/hep.24230"],"eki":["1814187103"]},"physDesc":[{"extent":"12 S."}],"language":["eng"],"title":[{"title":"Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk","title_sort":"Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk"}],"recId":"1814187103","origin":[{"dateIssuedKey":"2011","dateIssuedDisp":"11 February 2011"}],"name":{"displayForm":["Janka Mátrai, Alessio Cantore, Cynthia C. Bartholomae, Andrea Annoni, Wei Wang, Abel Acosta-Sanchez, Ermira Samara-Kuko, Liesbeth De Waele, Ling Ma, Pietro Genovese, Martina Damo, Anne Arens, Kevin Goudy, Timothy C. Nichols, Christof von Kalle, Marinee K.L. Chuah, Maria Grazia Roncarolo, Manfred Schmidt, Thierry VandenDriessche, and Luigi Naldini"]},"person":[{"role":"aut","family":"Mátrai","display":"Mátrai, Janka","given":"Janka"},{"role":"aut","family":"Cantore","given":"Alessio","display":"Cantore, Alessio"},{"family":"Bartholomae","given":"Cynthia C.","display":"Bartholomae, Cynthia C.","role":"aut"},{"given":"Andrea","display":"Annoni, Andrea","family":"Annoni","role":"aut"},{"role":"aut","display":"Wang, Wei","given":"Wei","family":"Wang"},{"role":"aut","family":"Acosta-Sanchez","given":"Abel","display":"Acosta-Sanchez, Abel"},{"display":"Samara-Kuko, Ermira","given":"Ermira","family":"Samara-Kuko","role":"aut"},{"given":"Liesbeth","display":"De Waele, Liesbeth","family":"De Waele","role":"aut"},{"role":"aut","display":"Ma, Ling","given":"Ling","family":"Ma"},{"role":"aut","given":"Pietro","display":"Genovese, Pietro","family":"Genovese"},{"role":"aut","given":"Martina","display":"Damo, Martina","family":"Damo"},{"given":"Anne","display":"Arens, Anne","family":"Arens","role":"aut"},{"family":"Goudy","given":"Kevin","display":"Goudy, Kevin","role":"aut"},{"role":"aut","given":"Timothy C.","display":"Nichols, Timothy C.","family":"Nichols"},{"role":"aut","display":"Kalle, Christof von","given":"Christof von","family":"Kalle"},{"family":"L. Chuah","given":"Marinee K.","display":"L. Chuah, Marinee K.","role":"aut"},{"role":"aut","display":"Roncarolo, Maria Grazia","given":"Maria Grazia","family":"Roncarolo"},{"role":"aut","family":"Schmidt","given":"Manfred","display":"Schmidt, Manfred"},{"given":"Thierry","display":"VandenDriessche, Thierry","family":"VandenDriessche","role":"aut"},{"role":"aut","family":"Naldini","given":"Luigi","display":"Naldini, Luigi"}]} | ||
| SRT | |a MATRAIJANKHEPATOCYTE1120 | ||