LNA-mediated microRNA silencing in non-human primates

Joacim Elmén, Morten Lindow, Sylvia Schütz, Matthew Lawrence, Andreas Petri, Susanna Obad, Marie Lindholm, Maj Hedtjärn, Henrik Frydenlund Hansen, Urs Berger, Steven Gullans, Phil Kearney, Peter Sarnow, Ellen Marie Straarup and Sakari Kauppinen ()
Additional contact information
Joacim Elmén: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark
Morten Lindow: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark
Sylvia Schütz: 299 Campus Drive, Stanford University School of Medicine, Stanford, California 94305, USA
Matthew Lawrence: RxGen Inc, 100 Deepwood Drive, Hamden, Connecticut 06517, USA
Andreas Petri: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark
Susanna Obad: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark
Marie Lindholm: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark
Maj Hedtjärn: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark
Henrik Frydenlund Hansen: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark
Urs Berger: UB-in situ, PO Box 463, Natick, Massachusetts 01760, USA
Steven Gullans: RxGen Inc, 100 Deepwood Drive, Hamden, Connecticut 06517, USA
Phil Kearney: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark
Peter Sarnow: 299 Campus Drive, Stanford University School of Medicine, Stanford, California 94305, USA
Ellen Marie Straarup: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark
Sakari Kauppinen: Santaris Pharma, Bøge Allé 3, DK-2970 Hørsholm, Denmark

Nature, 2008, vol. 452, issue 7189, 896-899

Abstract: 'Therapeutic' microRNA The realization that microRNAs play a central role in gene regulation in both normal development and disease, such as cancer, cardiac disease and metabolic disorders, suggests that they might be viable targets for therapeutic intervention. Now, for the first time, efficient, long-lasting and reversible microRNA silencing has been achieved in non-human primates. African green monkeys received intraperitoneal injections of a short modified DNA sequence that binds to and blocks the function of miR-122, a microRNA that regulates genes that influence cholesterol levels. Dose-dependent lowering of blood cholesterol followed, with no signs of toxicity. It is still a giant leap to therapeutic applications and, as microRNAs can act on many genes, toxicity risks are considerable.

Date: 2008
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DOI: 10.1038/nature06783

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