Pharmacological Inhibition of a MicroRNA Family in Nonhuman Primates by a Seed-Targeting 8-Mer AntimiR

Veerle Rottiers; Susanna Obad; Andreas Petri; Robert McGarrah; Marie W. Lindholm; Joshua C. Black; Sumita Sinha; Robin J. Goody; Matthew S. Lawrence; Andrew S. deLemos; Henrik F. Hansen; Steve Whittaker; Steve Henry; Rohn Brookes; Seyed Hani Najafi-Shoushtari; Raymond T. Chung; Johnathan R. Whetstine; Robert E. Gerszten; Sakari Kauppinen; Anders M. Näär

doi:10.1126/scitranslmed.3006840

Research ArticleMetabolic Syndrome

Pharmacological Inhibition of a MicroRNA Family in Nonhuman Primates by a Seed-Targeting 8-Mer AntimiR

Veerle Rottiers¹,²,*,
Susanna Obad³,*,
Andreas Petri³,⁴,
Robert McGarrah⁵,⁶,⁷,
Marie W. Lindholm³,
Joshua C. Black¹,⁸,
Sumita Sinha⁵,⁶,
Robin J. Goody⁹,
Matthew S. Lawrence⁹,
Andrew S. deLemos¹⁰,
Henrik F. Hansen³,
Steve Whittaker⁹,
Steve Henry⁹,
Rohn Brookes⁹,
Seyed Hani Najafi-Shoushtari¹,²,¹¹,
Raymond T. Chung¹⁰,
Johnathan R. Whetstine¹,⁸,
Robert E. Gerszten⁵,⁶,
Sakari Kauppinen³,⁴,† and
Anders M. Näär¹,²,†

¹Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
²Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
³Santaris Pharma, DK-2970 Hørsholm, Denmark.
⁴Department of Haematology, Aalborg University Hospital, DK-2450 Copenhagen SV, Denmark.
⁵Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
⁶Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁷Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
⁸Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
⁹RxGen Inc., 100 Deepwood Drive, Hamden, CT 06517, USA.
¹⁰Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
¹¹Department of Cell and Developmental Biology, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, P. O. Box 24144, Doha, Qatar.

↵†Corresponding author. E-mail: naar{at}helix.mgh.harvard.edu (A.M.N.); sk{at}bio.aau.dk (S.K.)

↵* These authors contributed equally to this work.

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Science Translational Medicine 20 Nov 2013:
Vol. 5, Issue 212, pp. 212ra162
DOI: 10.1126/scitranslmed.3006840

Veerle Rottiers

Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

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Susanna Obad

Santaris Pharma, DK-2970 Hørsholm, Denmark.

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Andreas Petri

Santaris Pharma, DK-2970 Hørsholm, Denmark.Department of Haematology, Aalborg University Hospital, DK-2450 Copenhagen SV, Denmark.

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Robert McGarrah

Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

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Marie W. Lindholm

Santaris Pharma, DK-2970 Hørsholm, Denmark.

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Joshua C. Black

Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

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Sumita Sinha

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Robin J. Goody

RxGen Inc., 100 Deepwood Drive, Hamden, CT 06517, USA.

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Matthew S. Lawrence

RxGen Inc., 100 Deepwood Drive, Hamden, CT 06517, USA.

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Andrew S. deLemos

Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

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Henrik F. Hansen

Santaris Pharma, DK-2970 Hørsholm, Denmark.

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Steve Whittaker

RxGen Inc., 100 Deepwood Drive, Hamden, CT 06517, USA.

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Steve Henry

RxGen Inc., 100 Deepwood Drive, Hamden, CT 06517, USA.

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Rohn Brookes

RxGen Inc., 100 Deepwood Drive, Hamden, CT 06517, USA.

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Seyed Hani Najafi-Shoushtari

Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.Department of Cell and Developmental Biology, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, P. O. Box 24144, Doha, Qatar.

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Raymond T. Chung

Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

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Johnathan R. Whetstine

Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

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Robert E. Gerszten

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Sakari Kauppinen

Santaris Pharma, DK-2970 Hørsholm, Denmark.Department of Haematology, Aalborg University Hospital, DK-2450 Copenhagen SV, Denmark.

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For correspondence: naar@helix.mgh.harvard.edu sk@bio.aau.dk

Anders M. Näär

Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

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For correspondence: naar@helix.mgh.harvard.edu sk@bio.aau.dk

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Long-term treatment of obese, insulin-resistant nonhuman primates with a seed-targeting antimiR oligonucleotide against the microRNA-33 family derepresses hepatic expression of miR-33 targets, increases circulating HDL cholesterol, and has a clean safety profile.

Pharmacological Inhibition of a MicroRNA Family in Nonhuman Primates by a Seed-Targeting 8-Mer AntimiR

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