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Institute of Physiology and Pathophysiology

Decoy oligodeoxynucleotides for the prevention of heart failure

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This research field aims at preclinically validating decoy oligodeoxynucleotides (ODNs) as a novel class of therapeutic drugs to prevent or treat heart failure.

    

Decoy ODNs, typically 15 to 20 base pairs short double-stranded DNA molecules, mimic the DNA binding site of specific regulatory proteins (transcription factors) in the genome. They interfere with the, in most cases, aberrant expression of disease-related genes by specifically binding to and, as a consequence, blocking the transcription factor controlling their expression.

 

Three different potential transcription factor drug targets are investigated. The most important criterion for choosing them is their proven involvement in the expression of genes primarily responsible for the development of various forms of terminal heart failure.

 

Members of the Division of Cardiovascular Physiology work on the design and optimization of the respective decoy ODNs. In collaboration with other groups at Heidelberg University  in vitro and in vivo model systems for the evaluation of their efficacy have been developed.

 

   

 

Aggregates of rat cardiomyocytes loaded with fluorescent decoy ODNs (red) (cell nuclei: blue)


Recent Publications

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The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms. J Cereb Blood Flow Metab. 2019 Nov 13:271678X19887777. doi: 10.1177/0271678X19887777. [Epub ahead of print]

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Shaping the heart: Structural and functional maturation of iPSC-cardiomyocytes in 3D-micro-scaffolds. Biomaterials. 2020 Jan;227:119551. doi: 10.1016/j.biomaterials.2019.119551. Epub 2019 Oct 19.

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Simulation Strategies for Calcium Microdomains and Calcium Noise. Adv Exp Med Biol. 2020;1131:771-797. doi: 10.1007/978-3-030-12457-1_31.

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Somatic mutations and promotor methylation of the ryanodine receptor 2 is a common event in the pathogenesis of head and neck cancer. Int J Cancer. 2019 Dec 15;145(12):3299-3310. doi: 10.1002/ijc.32481. Epub 2019 Jun 19.

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Persistent increase in ventral hippocampal long-term potentiation by juvenile stress: A role for astrocytic glutamine synthetase. Glia. 2019 Dec;67(12):2279-2293. doi: 10.1002/glia.23683. Epub 2019 Jul 17.

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4.2 Kreislauf. In: Physiologie hoch2 (Gründer S, Schlüter KD, eds.) Urban & Fischer Verlag/Elsevier GmbH 2019, pp. 192-225. ISBN 978-3-437-43461-7

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The neuronal oxygen-sensing pathway controls postnatal vascularization of the murine brain. FASEB J. 2019 Nov;33(11):12812-12824. doi: 10.1096/fj.201901385RR. Epub 2019 Aug 30.

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TRPC channels are not required for graded persistent activity in entorhinal cortex neurons. Hippocampus. 2019 Nov;29(11):1038-1048. doi: 10.1002/hipo.23094. Epub 2019 Apr 19.

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The C-terminal HCN4 variant P883R alters channel properties and acts as genetic modifier of atrial fibrillation and structural heart disease. Biochem Biophys Res Commun. 2019 Oct 29;519(1):141-147. doi: 10.1016/j.bbrc.2019.08.150. Epub 2019 Aug 31.

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Endothelial cell modulation of cardiomyocyte gene expression. Exp Cell Res. 2019 Oct 15;383(2):111565. doi: 10.1016/j.yexcr.2019.111565. Epub 2019 Aug 20.

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Pacemaker cell characteristics of differentiated and HCN4-transduced human mesenchymal stem cells. Life Sci. 2019 Sep 1;232:116620. doi: 10.1016/j.lfs.2019.116620. Epub 2019 Jul 7.

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Reduction of Transplant Vasculopathy by Intraoperative Nucleic Acid-based Therapy in a Mouse Aortic Allograft Model. Thorac Cardiovasc Surg. 2019 Sep;67(6):503-512. doi: 10.1055/s-0038-1673633. Epub 2018 Oct 23.

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Functional association of a CD40 gene single nucleotide polymorphism with the pathogenesis of coronary heart disease. Cardiovasc Res. 2019 Aug 2. pii: cvz206. doi: 10.1093/cvr/cvz206. [Epub ahead of print]


Institute of
Physiology and Pathophysiology

Heidelberg University

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone:+49 6221 54-4035
Fax:+49 6221 54-4038
E-mail:sekretariat.hecker@
physiologie.uni-heidelberg.de