Delivery of small interfering RNA (siRNA) has been one of the major hurdles for the application of RNA interference in therapeutics. Here, we describe a cationic lipid assisted polymeric nanoparticle system with stealthy property for efficient siRNA encapsulation and delivery, which was fabricated with poly(ethylene glycol)-b-poly(d,l-lactide), siRNA and a cationic lipid, using a double emulsion-solvent evaporation technique. By incorporation of the cationic lipid, the encapsulation efficiency of siRNA into the nanoparticles could be above 90% and the siRNA loading weight ratio was up to 4.47%, while the diameter of the nanoparticles was around 170 to 200 nm. The siRNA retained its integrity within the nanoparticles, which were effectively internalized by cancer cells and escaped from the endosome, resulting in significant gene knockdown. This effect was demonstrated by significant down-regulation of luciferase expression in HepG2-luciferase cells which stably express luciferase, and suppression of polo-like kinase 1 (Plk1) expression in HepG2 cells, following delivery of specific siRNAs by the nanoparticles. Furthermore, the nanoparticles carrying siRNA targeting the Plk1 gene were found to induce remarkable apoptosis in both HepG2 and MDA-MB-435s cancer cells. Systemic delivery of specific siRNA by nanoparticles significantly inhibited luciferase expression in an orthotopic murine liver cancer model and suppressed tumor growth in a MDA-MB-435s murine xenograft model, suggesting its therapeutic promise in disease treatment. (C) 2011 Elsevier B. V. All rights reserved.
机构:
Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Akinc, Akin
;
Zumbuehl, Andreas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Geneva, Dept Organ Chem, CH-1211 Geneva 4, Switzerland
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Zumbuehl, Andreas
;
Goldberg, Michael
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MIT, Dept Chem, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Goldberg, Michael
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Leshchiner, Elizaveta S.
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MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Leshchiner, Elizaveta S.
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Busini, Valentina
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MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Busini, Valentina
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Hossain, Naushad
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MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Hossain, Naushad
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Bacallado, Sergio A.
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MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Bacallado, Sergio A.
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Nguyen, David N.
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MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Nguyen, David N.
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Fuller, Jason
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MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Fuller, Jason
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Alvarez, Rene
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Alvarez, Rene
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Borodovsky, Anna
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Borland, Todd
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Borland, Todd
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Constien, Rainer
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Alnylam Europe AG, D-95326 Kulmbach, GermanyAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Constien, Rainer
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de Fougerolles, Antonin
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
de Fougerolles, Antonin
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Dorkin, J. Robert
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Dorkin, J. Robert
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
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Alnylam Europe AG, D-95326 Kulmbach, GermanyAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
John, Matthias
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Koteliansky, Victor
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Koteliansky, Victor
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Nechev, Lubomir
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Qin, June
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Qin, June
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Racie, Timothy
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Racie, Timothy
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Raitcheva, Denitza
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Raitcheva, Denitza
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Rajeev, Kallanthottathil G.
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Rajeev, Kallanthottathil G.
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Sah, Dinah W. Y.
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Sah, Dinah W. Y.
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Soutschek, Juergen
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Alnylam Europe AG, D-95326 Kulmbach, GermanyAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Soutschek, Juergen
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Toudjarska, Ivanka
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Toudjarska, Ivanka
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Vornlocher, Hans-Peter
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Alnylam Europe AG, D-95326 Kulmbach, GermanyAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
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Zimmermann, Tracy S.
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Zimmermann, Tracy S.
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Langer, Robert
论文数: 0引用数: 0
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MIT, Dept Chem, Cambridge, MA 02139 USA
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Langer, Robert
;
Anderson, Daniel G.
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MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
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City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, City Hope Grad Sch Biol Sci, Duarte, CA 91010 USACity Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA
Castanotto, Daniela
;
Rossi, John J.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, City Hope Grad Sch Biol Sci, Duarte, CA 91010 USACity Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA
机构:
CALTECH, Pasadena, CA 91125 USACALTECH, Pasadena, CA 91125 USA
Davis, Mark E.
;
Zuckerman, Jonathan E.
论文数: 0引用数: 0
h-index: 0
机构:
CALTECH, Pasadena, CA 91125 USACALTECH, Pasadena, CA 91125 USA
Zuckerman, Jonathan E.
;
Choi, Chung Hang J.
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h-index: 0
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CALTECH, Pasadena, CA 91125 USACALTECH, Pasadena, CA 91125 USA
Choi, Chung Hang J.
;
Seligson, David
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USACALTECH, Pasadena, CA 91125 USA
Seligson, David
;
Tolcher, Anthony
论文数: 0引用数: 0
h-index: 0
机构:
START LLC, San Antonio, TX 78229 USACALTECH, Pasadena, CA 91125 USA
Tolcher, Anthony
;
Alabi, Christopher A.
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h-index: 0
机构:
CALTECH, Pasadena, CA 91125 USACALTECH, Pasadena, CA 91125 USA
Alabi, Christopher A.
;
Yen, Yun
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h-index: 0
机构:
City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USACALTECH, Pasadena, CA 91125 USA
Yen, Yun
;
Heidel, Jeremy D.
论文数: 0引用数: 0
h-index: 0
机构:
Calando Pharmaceut, Pasadena, CA 91101 USACALTECH, Pasadena, CA 91125 USA
Heidel, Jeremy D.
;
Ribas, Antoni
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USACALTECH, Pasadena, CA 91125 USA
机构:
Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Akinc, Akin
;
Zumbuehl, Andreas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Geneva, Dept Organ Chem, CH-1211 Geneva 4, Switzerland
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Zumbuehl, Andreas
;
Goldberg, Michael
论文数: 0引用数: 0
h-index: 0
机构:
MIT, Dept Chem, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Goldberg, Michael
;
Leshchiner, Elizaveta S.
论文数: 0引用数: 0
h-index: 0
机构:
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Leshchiner, Elizaveta S.
;
Busini, Valentina
论文数: 0引用数: 0
h-index: 0
机构:
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Busini, Valentina
;
Hossain, Naushad
论文数: 0引用数: 0
h-index: 0
机构:
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Hossain, Naushad
;
Bacallado, Sergio A.
论文数: 0引用数: 0
h-index: 0
机构:
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Bacallado, Sergio A.
;
Nguyen, David N.
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MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Nguyen, David N.
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Fuller, Jason
论文数: 0引用数: 0
h-index: 0
机构:
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Fuller, Jason
;
Alvarez, Rene
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机构:
Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Alvarez, Rene
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Borodovsky, Anna
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Borodovsky, Anna
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Borland, Todd
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机构:
Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Borland, Todd
;
Constien, Rainer
论文数: 0引用数: 0
h-index: 0
机构:
Alnylam Europe AG, D-95326 Kulmbach, GermanyAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Constien, Rainer
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de Fougerolles, Antonin
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h-index: 0
机构:
Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
de Fougerolles, Antonin
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机构:
Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Dorkin, J. Robert
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Jayaprakash, K. Narayanannair
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Jayaprakash, K. Narayanannair
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Jayaraman, Muthusamy
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John, Matthias
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h-index: 0
机构:
Alnylam Europe AG, D-95326 Kulmbach, GermanyAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
John, Matthias
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Koteliansky, Victor
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h-index: 0
机构:
Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Koteliansky, Victor
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Manoharan, Muthiah
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Nechev, Lubomir
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Qin, June
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Racie, Timothy
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Raitcheva, Denitza
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Rajeev, Kallanthottathil G.
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机构:
Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Sah, Dinah W. Y.
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Alnylam Europe AG, D-95326 Kulmbach, GermanyAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Soutschek, Juergen
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Toudjarska, Ivanka
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机构:
Alnylam Europe AG, D-95326 Kulmbach, GermanyAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Vornlocher, Hans-Peter
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Zimmermann, Tracy S.
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Alnylam Pharmaceut Inc, Cambridge, MA 02142 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Zimmermann, Tracy S.
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Langer, Robert
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机构:
MIT, Dept Chem, Cambridge, MA 02139 USA
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
Langer, Robert
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Anderson, Daniel G.
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机构:
MIT, David H Koch Inst Integrat Canc Res, Dept Chem Engn, Cambridge, MA 02139 USAAlnylam Pharmaceut Inc, Cambridge, MA 02142 USA
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City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, City Hope Grad Sch Biol Sci, Duarte, CA 91010 USACity Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA
Castanotto, Daniela
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Rossi, John J.
论文数: 0引用数: 0
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机构:
City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA
City Hope Natl Med Ctr, Beckman Res Inst, City Hope Grad Sch Biol Sci, Duarte, CA 91010 USACity Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA
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CALTECH, Pasadena, CA 91125 USACALTECH, Pasadena, CA 91125 USA
Davis, Mark E.
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Zuckerman, Jonathan E.
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CALTECH, Pasadena, CA 91125 USACALTECH, Pasadena, CA 91125 USA
Zuckerman, Jonathan E.
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Choi, Chung Hang J.
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CALTECH, Pasadena, CA 91125 USACALTECH, Pasadena, CA 91125 USA
Choi, Chung Hang J.
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Seligson, David
论文数: 0引用数: 0
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机构:
Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USACALTECH, Pasadena, CA 91125 USA
Seligson, David
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Tolcher, Anthony
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START LLC, San Antonio, TX 78229 USACALTECH, Pasadena, CA 91125 USA
Tolcher, Anthony
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Alabi, Christopher A.
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机构:
CALTECH, Pasadena, CA 91125 USACALTECH, Pasadena, CA 91125 USA
Alabi, Christopher A.
;
Yen, Yun
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USACALTECH, Pasadena, CA 91125 USA
Yen, Yun
;
Heidel, Jeremy D.
论文数: 0引用数: 0
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机构:
Calando Pharmaceut, Pasadena, CA 91101 USACALTECH, Pasadena, CA 91125 USA
Heidel, Jeremy D.
;
Ribas, Antoni
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USACALTECH, Pasadena, CA 91125 USA