共 53 条
A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice
被引:201
作者:

Brown, Brian D.
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机构:
Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Cantore, Alessio
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机构:
Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Annoni, Andrea
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机构:
Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Sergi, Lucia Sergi
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机构:
Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Lombardo, Angelo
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Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Della Valle, Patrizia
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机构:
Hosp San Raffaele, IRCCS, Fdn Ctr San Raffaele Del Monte Tabor, Coagulat Serv & Thrombosis Res Unit, I-20132 Milan, Italy Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

D'Angelo, Armando
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h-index: 0
机构:
Hosp San Raffaele, IRCCS, Fdn Ctr San Raffaele Del Monte Tabor, Coagulat Serv & Thrombosis Res Unit, I-20132 Milan, Italy Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Naldini, Luigi
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h-index: 0
机构:
Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy
Univ Vita Salute San Raffaele, Milan, Italy Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy
机构:
[1] Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy
[2] Hosp San Raffaele, IRCCS, Fdn Ctr San Raffaele Del Monte Tabor, Coagulat Serv & Thrombosis Res Unit, I-20132 Milan, Italy
[3] Univ Vita Salute San Raffaele, Milan, Italy
来源:
关键词:
D O I:
10.1182/blood-2007-03-078493
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
A longstanding goal for the treatment of hemophilia B is the development of a gene transfer strategy that can maintain sustained production of clotting factor IX (FIX) in the absence of an immune response. To this end, we have sought to use lentiviral vectors (LVs) as a means for systemic gene transfer. Unfortunately, initial evaluation of LVs expressing F.IX from hepatocyte-specific promoters failed to achieve sustained F.IX expression in hemophilia B mice due to the induction of an anti-F.IX cellular immune response. Further analysis suggested that this may be a result of off-target transgene expression in hematopoietic-lineage cells of the spleen. In order to overcome this problem, we modified our vector to contain a target sequence for the hematopoietic-specific microRNA, miR-142-3p. This eliminated off-target expression in hematopoietic cells, and enabled sustained gene transfer in hemophilia B mice for more than 280 days after injection. Treated mice had more than 10% normal F.IX activity, no detectable anti-F.IX antibodies, and were unresponsive to F.IX immunization. Importantly, the mice survived tail-clip challenge, thus demonstrating phenotypic correction of their bleeding diathesis. This work, which is among the first applications to exploit the microRNA regulatory pathway, provides the basis for a promising new therapy for the treatment of hemophilia B.
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页码:4144 / 4152
页数:9
相关论文
共 53 条
[1]
Coordinate dual-gene transgenesis by lentiviral vectors carrying synthetic bidirectional promoters
[J].
Amendola, M
;
Venneri, MA
;
Biffi, A
;
Vigna, E
;
Naldini, L
.
NATURE BIOTECHNOLOGY,
2005, 23 (01)
:108-116

Amendola, M
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy HSR TIGET, I-20132 Milan, Italy

Venneri, MA
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy HSR TIGET, I-20132 Milan, Italy

Biffi, A
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy HSR TIGET, I-20132 Milan, Italy

Vigna, E
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy HSR TIGET, I-20132 Milan, Italy

Naldini, L
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy HSR TIGET, I-20132 Milan, Italy
[2]
Dendritic cells as therapeutic vaccines against cancer
[J].
Banchereau, J
;
Palucka, AK
.
NATURE REVIEWS IMMUNOLOGY,
2005, 5 (04)
:296-306

Banchereau, J
论文数: 0 引用数: 0
h-index: 0
机构:
Baylor Inst Immunol Res, Dallas, TX 75204 USA Baylor Inst Immunol Res, Dallas, TX 75204 USA

Palucka, AK
论文数: 0 引用数: 0
h-index: 0
机构:
Baylor Inst Immunol Res, Dallas, TX 75204 USA Baylor Inst Immunol Res, Dallas, TX 75204 USA
[3]
Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs
[J].
Bartel, DP
;
Chen, CZ
.
NATURE REVIEWS GENETICS,
2004, 5 (05)
:396-400

Bartel, DP
论文数: 0 引用数: 0
h-index: 0
机构: Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

Chen, CZ
论文数: 0 引用数: 0
h-index: 0
机构: Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[4]
Permanent partial phenotypic correction and tolerance in a mouse model of hemophilia B by stem cell gene delivery of human factor IX
[J].
Bigger, BW
;
Siapati, EK
;
Mistry, A
;
Waddington, SN
;
Nivsarkar, MS
;
Jacobs, L
;
Perrett, R
;
Holder, MV
;
Ridler, C
;
Kemball-Cook, G
;
Ali, RR
;
Forbes, SJ
;
Coutelle, C
;
Wright, N
;
Alison, M
;
Thrasher, AJ
;
Bonnet, D
;
Themis, M
.
GENE THERAPY,
2006, 13 (02)
:117-126

Bigger, BW
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Siapati, EK
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Mistry, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Waddington, SN
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Nivsarkar, MS
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Jacobs, L
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Perrett, R
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Holder, MV
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Ridler, C
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Kemball-Cook, G
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Ali, RR
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Forbes, SJ
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Coutelle, C
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Wright, N
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Alison, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Thrasher, AJ
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Bonnet, D
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England

Themis, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ London Imperial Coll Sci & Technol, Fac Med, Gene Therapy Res Grp, London, England
[5]
The MET oncogene drives a genetic programme linking cancer to haemostasis
[J].
Boccaccio, C
;
Sabatino, G
;
Medico, E
;
Girolami, F
;
Follenzi, A
;
Reato, G
;
Sottile, A
;
Naldini, L
;
Comoglio, PM
.
NATURE,
2005, 434 (7031)
:396-400

Boccaccio, C
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy

Sabatino, G
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy

Medico, E
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy

Girolami, F
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy

Follenzi, A
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy

Reato, G
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy

论文数: 引用数:
h-index:
机构:

Naldini, L
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy

Comoglio, PM
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy Univ Turin, Sch Med, Inst Canc Res & Treatment, Div Mol Oncol, I-10060 Turin, Italy
[6]
Factors influencing therapeutic efficacy and the host immune response to helper-dependent adenoviral gene therapy in hemophilia A mice
[J].
Brown, BD
;
Shi, CX
;
Rawle, FEM
;
Tinlin, S
;
McKinven, A
;
Hough, C
;
Graham, FL
;
Lillicrap, D
.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS,
2004, 2 (01)
:111-118

Brown, BD
论文数: 0 引用数: 0
h-index: 0
机构: Queens Univ, Dept Pathol & Mol Med, Richardson Lab, Kingston, ON K7L 3N6, Canada

Shi, CX
论文数: 0 引用数: 0
h-index: 0
机构: Queens Univ, Dept Pathol & Mol Med, Richardson Lab, Kingston, ON K7L 3N6, Canada

Rawle, FEM
论文数: 0 引用数: 0
h-index: 0
机构: Queens Univ, Dept Pathol & Mol Med, Richardson Lab, Kingston, ON K7L 3N6, Canada

Tinlin, S
论文数: 0 引用数: 0
h-index: 0
机构: Queens Univ, Dept Pathol & Mol Med, Richardson Lab, Kingston, ON K7L 3N6, Canada

McKinven, A
论文数: 0 引用数: 0
h-index: 0
机构: Queens Univ, Dept Pathol & Mol Med, Richardson Lab, Kingston, ON K7L 3N6, Canada

Hough, C
论文数: 0 引用数: 0
h-index: 0
机构: Queens Univ, Dept Pathol & Mol Med, Richardson Lab, Kingston, ON K7L 3N6, Canada

Graham, FL
论文数: 0 引用数: 0
h-index: 0
机构: Queens Univ, Dept Pathol & Mol Med, Richardson Lab, Kingston, ON K7L 3N6, Canada

Lillicrap, D
论文数: 0 引用数: 0
h-index: 0
机构:
Queens Univ, Dept Pathol & Mol Med, Richardson Lab, Kingston, ON K7L 3N6, Canada Queens Univ, Dept Pathol & Mol Med, Richardson Lab, Kingston, ON K7L 3N6, Canada
[7]
Dangerous liaisons: the role of "danger" signals in the immune response to gene therapy
[J].
Brown, BD
;
Lillicrap, D
.
BLOOD,
2002, 100 (04)
:1133-1140

Brown, BD
论文数: 0 引用数: 0
h-index: 0
机构:
Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada

Lillicrap, D
论文数: 0 引用数: 0
h-index: 0
机构:
Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada
[8]
In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance
[J].
Brown, Brian D.
;
Sitia, Giovanni
;
Annoni, Andrea
;
Hauben, Ehud
;
Sergi, Lucia Sergi
;
Zingale, Anna
;
Roncarolo, Maria Grazia
;
Guidotti, Luca G.
;
Naldini, Luigi
.
BLOOD,
2007, 109 (07)
:2797-2805

Brown, Brian D.
论文数: 0 引用数: 0
h-index: 0
机构: Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Sitia, Giovanni
论文数: 0 引用数: 0
h-index: 0
机构: Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Annoni, Andrea
论文数: 0 引用数: 0
h-index: 0
机构: Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Hauben, Ehud
论文数: 0 引用数: 0
h-index: 0
机构: Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Sergi, Lucia Sergi
论文数: 0 引用数: 0
h-index: 0
机构: Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Zingale, Anna
论文数: 0 引用数: 0
h-index: 0
机构: Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Roncarolo, Maria Grazia
论文数: 0 引用数: 0
h-index: 0
机构: Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Guidotti, Luca G.
论文数: 0 引用数: 0
h-index: 0
机构: Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy

Naldini, Luigi
论文数: 0 引用数: 0
h-index: 0
机构: Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy
[9]
Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer
[J].
Brown, Brian D.
;
Venneri, Mary Anna
;
Zingale, Anna
;
Sergi, Lucia Sergi
;
Naldini, Luigi
.
NATURE MEDICINE,
2006, 12 (05)
:585-591

Brown, Brian D.
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy, HSR TIGET, I-20132 Milan, Italy

Venneri, Mary Anna
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy, HSR TIGET, I-20132 Milan, Italy

Zingale, Anna
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy, HSR TIGET, I-20132 Milan, Italy

Sergi, Lucia Sergi
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy, HSR TIGET, I-20132 Milan, Italy

Naldini, Luigi
论文数: 0 引用数: 0
h-index: 0
机构: San Raffaele Telethon Inst Gene Therapy, HSR TIGET, I-20132 Milan, Italy
[10]
Stem cell-derived erythroid cells mediate long-term systemic protein delivery
[J].
Chang, Alex H.
;
T Stephan, Matthias
;
Sadelain, Michel
.
NATURE BIOTECHNOLOGY,
2006, 24 (08)
:1017-1021

Chang, Alex H.
论文数: 0 引用数: 0
h-index: 0
机构: Mem Sloan Kettering Canc Ctr, Lab Gene Transfer & Gene Express, New York, NY 10021 USA

T Stephan, Matthias
论文数: 0 引用数: 0
h-index: 0
机构: Mem Sloan Kettering Canc Ctr, Lab Gene Transfer & Gene Express, New York, NY 10021 USA

Sadelain, Michel
论文数: 0 引用数: 0
h-index: 0
机构: Mem Sloan Kettering Canc Ctr, Lab Gene Transfer & Gene Express, New York, NY 10021 USA