Full Text Journal Articles by
Author Sven Klussmann

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Neutralizing Complement C5a Protects Mice with Pneumococcal Pulmonary Sepsis.

Holger Müller-Redetzky, Ute Kellermann, Sandra-Maria Wienhold, Birgitt Gutbier, Jasmin Lienau, Katharina Hellwig, Katrin Reppe, Eleftheria Letsiou, Thomas Tschernig, Markus Scholz, Peter Ahnert, Christian Maasch, Kai Hoehlig, Sven Klussmann, Axel Vater, Theresa C Firsching, Judith Hoppe, Norbert Suttorp, Martin Witzenrath,

BACKGROUND:Community-acquired pneumonia and associated sepsis cause high mortality despite antibiotic treatment. Uncontrolled inflammatory host responses contribute to the unfavorable outcome by driving lung and extrapulmonary organ failure. The complement fragment C5a holds significant proinflammatory functions and is associated with tissue damage in various inflammatory conditions. The authors hypothesized that C5a ... Read more >>

Anesthesiology (Anesthesiology)
[2020, 132(4):795-807]

Cited: 0 times

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CCL2/MCP-1 and CXCL12/SDF-1 blockade by L-aptamers improve pancreatic islet engraftment and survival in mouse.

Antonio Citro, Silvia Pellegrini, Erica Dugnani, Dirk Eulberg, Sven Klussmann, Lorenzo Piemonti,

The blockade of pro-inflammatory mediators is a successful approach to improve the engraftment after islet transplantation. L-aptamers are chemically synthesized, nonimmunogenic bio-stable oligonucleotides that bind and inhibit target molecules conceptually similar to antibodies. We aimed to evaluate if blockade-aptamer-based inhibitors of C-C Motif Chemokine Ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) and ... Read more >>

Am. J. Transplant. (American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons)
[2019, 19(11):3131-3138]

Cited: 0 times

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Nonenzymatic Polymerization into Long Linear RNA Templated by Liquid Crystal Self-Assembly.

Marco Todisco, Tommaso P Fraccia, Greg P Smith, Andrea Corno, Lucas Bethge, Sven Klussmann, Elvezia M Paraboschi, Rosanna Asselta, Diego Colombo, Giuliano Zanchetta, Noel A Clark, Tommaso Bellini,

Self-synthesizing materials, in which supramolecular structuring enhances the formation of new molecules that participate to the process, represent an intriguing notion to account for the first appearance of biomolecules in an abiotic Earth. We present here a study of the abiotic formation of interchain phosphodiester bonds in solutions of short ... Read more >>

ACS Nano (ACS nano)
[2018, 12(10):9750-9762]

Cited: 1 time

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CXCL12 blockade preferentially regenerates lost podocytes in cortical nephrons by targeting an intrinsic podocyte-progenitor feedback mechanism.

Simone Romoli, Maria Lucia Angelotti, Giulia Antonelli, Santhosh Kumar Vr, Shrikant R Mulay, Jyaysi Desai, Lidia Anguiano Gomez, Dana Thomasova, Dirk Eulberg, Sven Klussmann, Maria Elena Melica, Carolina Conte, Duccio Lombardi, Laura Lasagni, Hans-Joachim Anders, Paola Romagnani,

Insufficient podocyte regeneration after injury is a central pathomechanism of glomerulosclerosis and chronic kidney disease. Podocytes constitutively secrete the chemokine CXCL12, which is known to regulate homing and activation of stem cells; hence we hypothesized a similar effect of CXCL12 on podocyte progenitors. CXCL12 blockade increased podocyte numbers and attenuated ... Read more >>

Kidney Int. (Kidney international)
[2018, 94(6):1111-1126]

Cited: 4 times

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Newtonian to non-newtonian fluid transition of a model transient network.

Giovanni Nava, Tie Yang, Valerio Vitali, Paolo Minzioni, Ilaria Cristiani, Francesca Bragheri, Roberto Osellame, Lucas Bethge, Sven Klussmann, Elvezia Maria Paraboschi, Rosanna Asselta, Tommaso Bellini,

The viscosity of gel-forming fluids is notoriously complex and its study can benefit from new model systems that enable a detailed control of the network features. Here we use a novel and simple microfluidic-based active microrheology approach to study the transition from Newtonian to non-Newtonian behavior in a DNA hydrogel ... Read more >>

Soft Matter (Soft matter)
[2018, 14(17):3288-3295]

Cited: 1 time

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Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus.

Michael J M Fischer, Jakob Schmidt, Stanislav Koulchitsky, Sven Klussmann, Axel Vater, Karl Messlinger,

Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues including intracranial afferents, and their activity is thought to reflect facial pain and headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have ... Read more >>

J Headache Pain (The Journal of Headache and Pain)
[2018, 19(1):3]

Cited: 1 time

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Reprint of "Dual blockade of the pro-inflammatory chemokine CCL2 and the homeostatic chemokine CXCL12 is as effective as high dose cyclophosphamide in murine proliferative lupus nephritis".

Satish Kumar Devarapu, Santhosh Kumar Vr, Khader Valli Rupanagudi, Onkar P Kulkarni, Dirk Eulberg, Sven Klussmann, Hans-Joachim Anders,

Induction therapy of proliferative lupus nephritis still requires the use of unselective immunosuppressive drugs with significant toxicities. In search of more specific drugs with equal efficacy but fewer side effects we considered blocking pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and homeostatic chemokine stromal cell-derived factor-1 (SDF-1/CXCL12), which both contribute to ... Read more >>

Clin. Immunol. (Clinical immunology (Orlando, Fla.))
[2017, 185:119-127]

Cited: 1 time

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Novel Tumor Pretargeting System Based on Complementary l-Configured Oligonucleotides.

Maik Schubert, Ralf Bergmann, Christian Förster, Wiebke Sihver, Stefan Vonhoff, Sven Klussmann, Lucas Bethge, Martin Walther, Jörn Schlesinger, Jens Pietzsch, Jörg Steinbach, Hans-Jürgen Pietzsch,

Unnatural mirror image l-configured oligonucleotides (L-ONs) are a convenient substance class for the application as complementary in vivo recognition system between a tumor specific antibody and a smaller radiolabeled effector molecule in pretargeting approaches. The high hybridization velocity and defined melting conditions are excellent preconditions of the L-ON based methodology. ... Read more >>

Bioconjug. Chem. (Bioconjugate chemistry)
[2017, 28(4):1176-1188]

Cited: 2 times

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A thermostable d-polymerase for mirror-image PCR.

Andreas Pech, John Achenbach, Michael Jahnz, Simone Schülzchen, Florian Jarosch, Frank Bordusa, Sven Klussmann,

Biological evolution resulted in a homochiral world in which nucleic acids consist exclusively of d-nucleotides and proteins made by ribosomal translation of l-amino acids. From the perspective of synthetic biology, however, particularly anabolic enzymes that could build the mirror-image counterparts of biological macromolecules such as l-DNA or l-RNA are lacking. ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2017, 45(7):3997-4005]

Cited: 3 times

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Liquid Crystal Ordering and Isotropic Gelation in Solutions of Four-Base-Long DNA Oligomers.

Tommaso P Fraccia, Gregory P Smith, Lucas Bethge, Giuliano Zanchetta, Giovanni Nava, Sven Klussmann, Noel A Clark, Tommaso Bellini,

Liquid crystal ordering is reported in aqueous solutions of the oligomer 5'-ATTAp-3' and of the oligomer 5'-GCCGp-3'. In both systems, we quantitatively interpret ordering as stemming from the chaining of molecules via a "running-bond" type of pairing, a self-assembly process distinct from the duplex aggregation previously reported for longer oligonucleotides. ... Read more >>

ACS Nano (ACS nano)
[2016, 10(9):8508-8516]

Cited: 8 times

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Dual blockade of the pro-inflammatory chemokine CCL2 and the homeostatic chemokine CXCL12 is as effective as high dose cyclophosphamide in murine proliferative lupus nephritis.

Satish Kumar Devarapu, Santhosh Kumar Vr, Khader Valli Rupanagudi, Onkar P Kulkarni, Dirk Eulberg, Sven Klussmann, Hans-Joachim Anders,

Induction therapy of proliferative lupus nephritis still requires the use of unselective immunosuppressive drugs with significant toxicities. In search of more specific drugs with equal efficacy but fewer side effects we considered blocking pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and homeostatic chemokine stromal cell-derived factor-1 (SDF-1/CXCL12), which both contribute to ... Read more >>

Clin. Immunol. (Clinical immunology (Orlando, Fla.))
[2016, 169:139-147]

Cited: 5 times

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Expanding biohybrid-mediated asymmetric catalysis into the realm of RNA.

Nicolas Duchemin, Erica Benedetti, Lucas Bethge, Stefan Vonhoff, Sven Klussmann, Jean-Jacques Vasseur, Janine Cossy, Michael Smietana, Stellios Arseniyadis,

The recent development of biohybrid catalytic systems has allowed synthetic chemists to reach high levels of selectivity on a wide variety of valuable synthetic transformations. In this context, DNA-based catalysts have emerged as particularly appealing tools. Interestingly, while long RNA sequences (ribozymes) are known to catalyse specific biochemical reactions with ... Read more >>

Chem. Commun. (Camb.) (Chemical communications (Cambridge, England))
[2016, 52(55):8604-8607]

Cited: 5 times

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Noncompetitive affinity assays of glucagon and amylin using mirror-image aptamers as affinity probes.

Lian Yi, Xue Wang, Lucas Bethge, Sven Klussmann, Michael G Roper,

The ability to detect picomolar concentrations of glucagon and amylin using fluorescently labeled mirror-image aptamers, so-called Spiegelmers, is demonstrated. Spiegelmers rival the specificity of antibodies and overcome the problem of biostability of natural aptamers in a biological matrix. Using Spiegelmers as affinity probes, noncompetitive capillary electrophoresis affinity assays of glucagon ... Read more >>

Analyst (The Analyst)
[2016, 141(6):1939-1946]

Cited: 3 times

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SDF-1/CXCR4/CXCR7 is pivotal for vascular smooth muscle cell proliferation and chronic allograft vasculopathy.

Michael N Thomas, Aivars Kalnins, Martin Andrassy, Anne Wagner, Sven Klussmann, Markus Rentsch, Antje Habicht, Sebastian Pratschke, Manfred Stangl, Alexandr V Bazhin, Bruno Meiser, Michael Fischereder, Jens Werner, Markus Guba, Joachim Andrassy,

Chronic rejection remains a major obstacle in transplant medicine. Recent studies suggest a crucial role of the chemokine SDF-1 on neointima formation after injury. Here, we investigate the potential therapeutic effect of inhibiting the SDF-1/CXCR4/CXCR7 axis with an anti-SDF-1 Spiegelmer (NOX-A12) on the development of chronic allograft vasculopathy. Heterotopic heart ... Read more >>

Transpl. Int. (Transplant international : official journal of the European Society for Organ Transplantation)
[2015, 28(12):1426-1435]

Cited: 5 times

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Outwitting EF-Tu and the ribosome: translation with d-amino acids.

John Achenbach, Michael Jahnz, Lucas Bethge, Krisztina Paal, Maria Jung, Maja Schuster, Renate Albrecht, Florian Jarosch, Knud H Nierhaus, Sven Klussmann,

Key components of the translational apparatus, i.e. ribosomes, elongation factor EF-Tu and most aminoacyl-tRNA synthetases, are stereoselective and prevent incorporation of d-amino acids (d-aa) into polypeptides. The rare appearance of d-aa in natural polypeptides arises from post-translational modifications or non-ribosomal synthesis. We introduce an in vitro translation system that enables ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2015, 43(12):5687-5698]

Cited: 19 times

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Intravitreal inhibition of complement C5a reduces choroidal neovascularization in mice.

Claudia Brockmann, Tobias Brockmann, Sabrina Dege, Catharina Busch, Norbert Kociok, Axel Vater, Sven Klussmann, Olaf Strauß, Antonia M Joussen,

To investigate the influence of complement component C5a inhibition on laser-induced choroidal neovascularization (CNV) in mice using a C5a specific L-aptamer.In C57BL/6 J mice CNV was induced by argon-laser, C5a-inhibitor (NOX-D20) was intravitreally injected in three concentrations: 0.3, 3.0, and 30 mg/ml. The unPEGylated derivate (NOX-D20001) was applied at 3.0 ... Read more >>

Graefes Arch. Clin. Exp. Ophthalmol. (Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie)
[2015, 253(10):1695-1704]

Cited: 7 times

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Structural basis for the targeting of complement anaphylatoxin C5a using a mixed L-RNA/L-DNA aptamer.

Laure Yatime, Christian Maasch, Kai Hoehlig, Sven Klussmann, Gregers R Andersen, Axel Vater,

L-Oligonucleotide aptamers (Spiegelmers) consist of non-natural L-configured nucleotides and are of particular therapeutic interest due to their high resistance to plasma nucleases. The anaphylatoxin C5a, a potent inflammatory mediator generated during complement activation that has been implicated with organ damage, can be efficiently targeted by Spiegelmers. Here, we present the ... Read more >>

Nat Commun (Nature communications)
[2015, 6:6481]

Cited: 20 times

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DNA-cellulose: an economical, fully recyclable and highly effective chiral biomaterial for asymmetric catalysis.

Erica Benedetti, Nicolas Duchemin, Lucas Bethge, Stefan Vonhoff, Sven Klussmann, Jean-Jacques Vasseur, Janine Cossy, Michael Smietana, Stellios Arseniyadis,

The challenge in DNA-based asymmetric catalysis is to perform a reaction in the vicinity of the helix by incorporating a small-molecule catalyst anchored to the DNA in a covalent, dative, or non-covalent yet stable fashion in order to ensure high levels of enantio-discrimination. Here, we report the first generation of ... Read more >>

Chem. Commun. (Camb.) (Chemical communications (Cambridge, England))
[2015, 51(28):6076-6079]

Cited: 6 times

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Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2.

Dominik Oberthür, John Achenbach, Azat Gabdulkhakov, Klaus Buchner, Christian Maasch, Sven Falke, Dirk Rehders, Sven Klussmann, Christian Betzel,

We report the crystal structure of a 40 mer mirror-image RNA oligonucleotide completely built from nucleotides of the non-natural L-chirality in complex with the pro-inflammatory chemokine L-CLL2 (monocyte chemoattractant protein-1), a natural protein composed of regular L-amino acids. The L-oligonucleotide is an L-aptamer (a Spiegelmer) identified to bind L-CCL2 with ... Read more >>

Nat Commun (Nature communications)
[2015, 6:6923]

Cited: 28 times

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Stereospecificity of oligonucleotide interactions revisited: no evidence for heterochiral hybridization and ribozyme/DNAzyme activity.

Kai Hoehlig, Lucas Bethge, Sven Klussmann,

A major challenge for the application of RNA- or DNA-oligonucleotides in biotechnology and molecular medicine is their susceptibility to abundant nucleases. One intriguing possibility to tackle this problem is the use of mirror-image (l-)oligonucleotides. For aptamers, this concept has successfully been applied to even develop therapeutic agents, so-called Spiegelmers. However, ... Read more >>

PLoS ONE (PloS one)
[2015, 10(2):e0115328]

Cited: 2 times

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Neonatal ghrelin programs development of hypothalamic feeding circuits.

Sophie M Steculorum, Gustav Collden, Berengere Coupe, Sophie Croizier, Sarah Lockie, Zane B Andrews, Florian Jarosch, Sven Klussmann, Sebastien G Bouret,

A complex neural network regulates body weight and energy balance, and dysfunction in the communication between the gut and this neural network is associated with metabolic diseases, such as obesity. The stomach-derived hormone ghrelin stimulates appetite through interactions with neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2015, 125(2):846-858]

Cited: 43 times

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Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer(®) therapeutics.

Axel Vater, Sven Klussmann,

Spiegelmers are synthetic target-binding oligonucleotides built from non-natural l-nucleotides. Like aptamers, Spiegelmers fold into distinct shapes that bind the targets with high affinity and selectivity. Furthermore, the mirror-image configuration confers plasma stability and immunological passivity. Various Spiegelmers against pharmacologically attractive targets were shown to be efficacious in animal models. Three ... Read more >>

Drug Discov. Today (Drug discovery today)
[2015, 20(1):147-155]

Cited: 43 times

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SDF-1 inhibition targets the bone marrow niche for cancer therapy.

Aldo M Roccaro, Antonio Sacco, Werner G Purschke, Michele Moschetta, Klaus Buchner, Christian Maasch, Dirk Zboralski, Stefan Zöllner, Stefan Vonhoff, Yuji Mishima, Patricia Maiso, Michaela R Reagan, Silvia Lonardi, Marco Ungari, Fabio Facchetti, Dirk Eulberg, Anna Kruschinski, Axel Vater, Giuseppe Rossi, Sven Klussmann, Irene M Ghobrial,

Bone marrow (BM) metastasis remains one of the main causes of death associated with solid tumors as well as multiple myeloma (MM). Targeting the BM niche to prevent or modulate metastasis has not been successful to date. Here, we show that stromal cell-derived factor-1 (SDF-1/CXCL12) is highly expressed in active ... Read more >>

Cell Rep (Cell reports)
[2014, 9(1):118-128]

Cited: 40 times

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Identification and characterization of a mirror-image oligonucleotide that binds and neutralizes sphingosine 1-phosphate, a central mediator of angiogenesis.

Werner G Purschke, Kai Hoehlig, Klaus Buchner, Dirk Zboralski, Frank Schwoebel, Axel Vater, Sven Klussmann,

The sphingolipid S1P (sphingosine 1-phosphate) is known to be involved in a number of pathophysiological conditions such as cancer, autoimmune diseases and fibrosis. It acts extracellularly through a set of five G-protein-coupled receptors, but its intracellular actions are also well documented. Employing in vitro selection techniques, we identified an L-aptamer (Spiegelmer®) ... Read more >>

Biochem. J. (The Biochemical journal)
[2014, 462(1):153-162]

Cited: 9 times

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DNA vs. mirror-image DNA: a universal approach to tune the absolute configuration in DNA-based asymmetric catalysis.

Jocelyn Wang, Erica Benedetti, Lucas Bethge, Stefan Vonhoff, Sven Klussmann, Jean-Jacques Vasseur, Janine Cossy, Michael Smietana, Stellios Arseniyadis,

Mirror mirror on the wall: By taking advantage of the unique structural features of L-DNA, the first examples of left-helical enantioselective induction in the field of DNA-based asymmetric catalysis were realized. Most importantly, this approach is the only one that allows a reliable and predictable access to both enantiomers for ... Read more >>

Angew. Chem. Int. Ed. Engl. (Angewandte Chemie (International ed. in English))
[2013, 52(44):11546-11549]

Cited: 23 times

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