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

View ORCID ProfileNa Kong¹,²,*,
View ORCID ProfileWei Tao¹,*,†,
Xiang Ling¹,
View ORCID ProfileJunqing Wang¹,
Yuling Xiao¹,
Sanjun Shi¹,
Xiaoyuan Ji¹,³,
Aram Shajii¹,
Silvia Tian Gan¹,⁴,
View ORCID ProfileNa Yoon Kim¹,
View ORCID ProfileDan G. Duda⁵,
View ORCID ProfileTian Xie³,†,
View ORCID ProfileOmid C. Farokhzad¹,⁶,† and
View ORCID ProfileJinjun 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

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.

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ORCID record for Na Kong

Wei Tao

1Center 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

1Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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Junqing Wang

1Center 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 Junqing Wang

Yuling Xiao

1Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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Sanjun Shi

1Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

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Xiaoyuan Ji

1Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

3Department of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.

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Aram Shajii

1Center 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

1Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

4Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

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Na Yoon Kim

1Center 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

5Steele 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

3Department 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

1Center for Nanomedicine and Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

6King 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

1Center 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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