Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes p53-deficient cancers to mTOR inhibition

Na Kong; Wei Tao; Xiang Ling; Junqing Wang; Yuling Xiao; Sanjun Shi; Xiaoyuan Ji; Aram Shajii; Silvia Tian Gan; Na Yoon Kim; Dan G. Duda; Tian Xie; Omid C. Farokhzad; Jinjun Shi

doi:10.1126/scitranslmed.aaw1565

Research ArticleCancer

Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes p53-deficient cancers to mTOR inhibition

Na Kong¹,²,*,
Wei Tao¹,*,†,
Xiang Ling¹,
Junqing Wang¹,
Yuling Xiao¹,
Sanjun Shi¹,
Xiaoyuan Ji¹,³,
Aram Shajii¹,
Silvia Tian Gan¹,⁴,
Na Yoon Kim¹,
Dan G. Duda⁵,
Tian Xie³,†,
Omid C. Farokhzad¹,⁶,† and
Jinjun Shi ¹,†

¹Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
²School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
³Department of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
⁴Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
⁵Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁶King Abdulaziz University, Jeddah 21589, Saudi Arabia.

↵†Corresponding author. Email: wtao{at}bwh.harvard.edu (W.T.); tianxie{at}hznu.edu.cn (T.X.); ofarokhzad{at}bwh.harvard.edu (O.C.F.); jshi{at}bwh.harvard.edu (J.S.)

↵* These authors contributed equally to this work.

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Science Translational Medicine 18 Dec 2019:
Vol. 11, Issue 523, eaaw1565
DOI: 10.1126/scitranslmed.aaw1565

Na Kong

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.

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Wei Tao

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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ORCID record for Wei Tao
For correspondence: wtao@bwh.harvard.edu tianxie@hznu.edu.cn ofarokhzad@bwh.harvard.edu jshi@bwh.harvard.edu

Xiang Ling

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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Junqing Wang

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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Yuling Xiao

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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Sanjun Shi

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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Xiaoyuan Ji

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

Department of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.

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Aram Shajii

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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Silvia Tian Gan

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

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Na Yoon Kim

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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Dan G. Duda

Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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Tian Xie

Department of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.

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For correspondence: wtao@bwh.harvard.edu tianxie@hznu.edu.cn ofarokhzad@bwh.harvard.edu jshi@bwh.harvard.edu

Omid C. Farokhzad

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

King Abdulaziz University, Jeddah 21589, Saudi Arabia.

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For correspondence: wtao@bwh.harvard.edu tianxie@hznu.edu.cn ofarokhzad@bwh.harvard.edu jshi@bwh.harvard.edu

Jinjun Shi

Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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For correspondence: wtao@bwh.harvard.edu tianxie@hznu.edu.cn ofarokhzad@bwh.harvard.edu jshi@bwh.harvard.edu

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Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes p53-deficient cancers to mTOR inhibition

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