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Your search keyword '"Constien, Rainer"' showing total 9 results
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9 results on '"Constien, Rainer"'

1. Autoimmunity and Inflammation Due to a Gain-of-Function Mutation in Phospholipase Cγ2 that Specifically Increases External Ca 2+ Entry

Author

Yu, Philipp, Constien, Rainer, Dear, Neil, Katan, Matilda, Hanke, Petra, Bunney, Tom D., Kunder, Sandra, Quintanilla-Martinez, Leticia, Huffstadt, Ulrike, Schröder, Andreas, Jones, Neil P., Peters, Thomas, Fuchs, Helmut, Hrabe de Angelis, Martin, Nehls, Michael, Grosse, Johannes, Wabnitz, Philipp, Meyer, Thomas P.H., Yasuda, Kei, Schiemann, Matthias, Schneider-Fresenius, Christian, Jagla, Wolfgang, Russ, Andreas, Popp, Andreas, Josephs, Michelle, Marquardt, Andreas, Laufs, Jürgen, Schmittwolf, Carolin, Wagner, Hermann, Pfeffer, Klaus, and Mudde, Geert C.

Published
2005
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3. Autoimmunity and Inflammation Due to a Gain-of-Function Mutation in Phospholipase Cγ2 that Specifically Increases External Ca2+ Entry

Author

Yu, Philipp, Constien, Rainer, Dear, Neil, Katan, Matilda, Hanke, Petra, Bunney, Tom D., Kunder, Sandra, Quintanilla-Martinez, Leticia, Huffstadt, Ulrike, Schröder, Andreas, Jones, Neil P., Peters, Thomas, Fuchs, Helmut, Hrabe de Angelis, Martin, Nehls, Michael, Grosse, Johannes, Wabnitz, Philipp, Meyer, Thomas P.H., Yasuda, Kei, Schiemann, Matthias, Schneider-Fresenius, Christian, Jagla, Wolfgang, Russ, Andreas, Popp, Andreas, Josephs, Michelle, Marquardt, Andreas, Laufs, Jürgen, Schmittwolf, Carolin, Wagner, Hermann, Pfeffer, Klaus, and Mudde, Geert C.

Published
2005
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4. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs

Author

Soutschek, Jürgen, Akinc, Akin, Bramlage, Birgit, Charisse, Klaus, Constien, Rainer, Donoghue, Mary, Elbashir, Sayda, Geick, Anke, Hadwiger, Philipp, Harborth, Jens, John, Matthias, Kesavan, Venkitasamy, Lavine, Gary, Pandey, Rajendra K., Racie, Timothy, Rajeev, Kallanthottathil G., Röhl, Ingo, Toudjarska, Ivanka, Wang, Gang, Wuschko, Silvio, Bumcrot, David, Koteliansky, Victor, Limmer, Stefan, Manoharan, Muthiah, and Vornlocher, Hans-Peter

Published
2004

5. The Minipig is a Suitable Non-Rodent Model in the Safety Assessment of Single Stranded Oligonucleotides.

Author

Braendli-Baiocco, Annamaria, Festag, Matthias, Erichsen, Kamille Dumong, Persson, Robert, Mihatsch, Michael J., Fisker, Niels, Funk, Juergen, Mohr, Susanne, Constien, Rainer, Ploix, Corinne, Brady, Kevin, Berrera, Marco, Altmann, Bernd, Lenz, Barbara, Albassam, Mudher, Schmitt, Georg, Weiser, Thomas, Schuler, Franz, Singer, Thomas, and Tessier, Yann

Subjects
OLIGONUCLEOTIDES, RODENTS, TOXICOGENOMICS, DNA microarrays, WOUNDS & injuries
Abstract

Non-human primates (NHPs) are currently considered to be the non-rodent species of choice for the preclinical safety assessment of single-stranded oligonucleotide (SSO) drugs. We evaluated minipigs as a potential alternative to NHPs to test the safety of this class of compounds. Four different phosphorothioated locked nucleic acid-based SSOs (3 antisense and 1 anti-miR), all with known safety profiles, were administered to minipigs using similar study designs and read-outs as in earlier NHP studies with the same compounds. The studies included toxicokinetic investigations, in-lifemonitoring, clinical and anatomic pathology. In the minipig, we demonstrated target engagement by the SSOs where relevant, and a similar toxicokinetic behavior in plasma, kidney, and liver when compared with NHPs. Clinical tolerability was similar between minipig and NHPs. For the first time, we showed similar and dose-dependent effects on the coagulation and complement cascade after intravenous dosing similar to those observed in NHPs. Similar to NHPs, morphological changes were seen in proximal tubular epithelial cells of the kidney, Kupffer cells, hepatocytes, and lymph nodes. Minipigs appeared more sensitive to the high-dose kidney toxicity of most of the selected SSOs than NHPs. No new target organ or off-target toxicities were identified in the minipig. The minipig did not predict the clinical features of human injection site reactions better than the NHPs, but histopathological similarities were observed between minipigs and NHPs. We conclude that there is no impediment, as default, to the use of minipigs as the non-rodent species in SSO candidate non-clinical safety packages. [ABSTRACT FROM AUTHOR]

Published
2017
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6. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics.

Author

Akinc, Akin, Zumbuehl, Andreas, Goldberg, Michael, Leshchiner, Elizaveta S, Busini, Valentina, Hossain, Naushad, Bacallado, Sergio A, Nguyen, David N, Fuller, Jason, Alvarez, Rene, Borodovsky, Anna, Borland, Todd, Constien, Rainer, de Fougerolles, Antonin, Dorkin, J Robert, Narayanannair Jayaprakash, K, Jayaraman, Muthusamy, John, Matthias, Koteliansky, Victor, and Manoharan, Muthiah

Subjects
GENE silencing, SMALL interfering RNA, ANTISENSE RNA, LIPIDS, BIOTECHNOLOGY, BIOSYNTHESIS
Abstract

The safe and effective delivery of RNA interference (RNAi) therapeutics remains an important challenge for clinical development. The diversity of current delivery materials remains limited, in part because of their slow, multi-step syntheses. Here we describe a new class of lipid-like delivery molecules, termed lipidoids, as delivery agents for RNAi therapeutics. Chemical methods were developed to allow the rapid synthesis of a large library of over 1,200 structurally diverse lipidoids. From this library, we identified lipidoids that facilitate high levels of specific silencing of endogenous gene transcripts when formulated with either double-stranded small interfering RNA (siRNA) or single-stranded antisense 2′-O-methyl (2′-OMe) oligoribonucleotides targeting microRNA (miRNA). The safety and efficacy of lipidoids were evaluated in three animal models: mice, rats and nonhuman primates. The studies reported here suggest that these materials may have broad utility for both local and systemic delivery of RNA therapeutics. [ABSTRACT FROM AUTHOR]

Published
2008
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