RNA therapeutics; hydrophobic bases; chemically modified oligonucleotides; antisense agents; RNA damage
Roethlisberger Pascal, Kaliginediand Veerabhadrarao, Leumann Christian J. (2017), Modulation of Excess Electron Transfer through LUMO Gradients in DNA Containing Phenanthrenyl Base Surrogates, in Chemistry - A European Journal
, 23(9), 2022-2025.
Schuermann David, Scheidegger Simon P., Weber Alain R., Bjørås Magnar, Leumann Christian J., Schär Primo (2016), 3CAPS – a structural AP–site analogue as a tool to investigate DNA base excision repair, in Nucleic Acids Research
, 44, 2187-2198.
Hari Yvonne, Dugovič Branislav, Istrate Alena, Fignolé Annabel, Leumann Christian J., Schürch Stefan (2016), The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes, in Journal of the American Society for Mass Spectrometry
, 27, 1186-1196.
Goyenvalle Aurelie, Leumann Christian, Garcia Luis (2016), Therapeutic Potential of Tricyclo-DNA antisense oligonucleotides, in Journal of Neuromuscular Diseases
, 3, 157-167.
Roethlisberger P., Istrate A., Marcaida Lopez M. J., Visini R., Stocker A., Reymond J. L., Leumann C. J. (2016), X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair, in Chemical Communications
, 52, 4749-4752.
Istrate Alena, Medvecky Michal, Leumann Christian J. (2015), 2′-Fluorination of Tricyclo-DNA Controls Furanose Conformation and Increases RNA Affinity, in Organic Letters
, 17, 1950-1953.
Goyenvalle Aurelie, Griffith Graziella, Babbs Arran, Andaloussi Samir El, Ezzat Kariem, Avril Aurelie, Dugovic Branislav, Chaussenot Remi, Ferry Arnaud, Voit Thomas, Amthor Helge, Buhr Claudia, Schurch Stefan, Wood Matthew J. A., Davies Kay E., Vaillend Cyrille, Leumann Christian, Garcia Luis (2015), Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers, in Nat Med
, 21, 270-275.
Ezzat Kariem, Aoki Yoshitsugu, Koo Taeyoung, McClorey Graham, Benner Leif, Coenen-Stass Anna, O’Donovan Liz, Lehto Taavi, Garcia-Guerra Antonio, Nordin Joel, Saleh Amer F., Behlke Mark, Morris John, Goyenvalle Aurelie, Dugovic Branislav, Leumann Christian, Gordon Siamon, Gait Michael J., El−Andaloussi Samir, Wood Matthew J. A. (2015), Self-Assembly into Nanoparticles Is Essential for Receptor Mediated Uptake of Therapeutic Antisense Oligonucleotides, in Nano Letters
, 15, 4364-4373.
Medvecky Michal, Istrate Alena, Leumann Christian J. (2015), Synthesis and Properties of 6′-Fluoro-tricyclo-DNA, in Journal of Organic Chemistry
, 80, 3556-3565.
Calabretta Alessandro, Küpfer Pascal A., Leumann Christian J. (2015), The effect of RNA base lesions on mRNA translation, in Nucleic Acids Research
, 43, 4713-4720.
Imbert M., Griffith G., Benchaouir R., Beley C., Dugovic B., Leumann C., Garcia L., Goyenvalle A. (2015), Therapeutic strategies for Huntington's, in Human Gene Therapy
, 26, 80-81.
Dugovic Branislav, Leumann Christian J. (2014), A 6′-Fluoro-Substituent in Bicyclo-DNA Increases Affinity to Complementary RNA Presumably by CF–HC Pseudohydrogen Bonds, in Journal of Organic Chemistry
, 79, 1271-1279.
Goyenvalle A., Robin V., Garcia L., Dugovic B., Leumann C. J. (2014), O09 Tricyclo-DNA for the treatment of neuromuscular diseases, in Neuromuscular Disorders
, 24, Supplement 1, 3-3.
Küpfer PascalA, Leumann Christian (2014), Oxidative Damage on RNA Nucleobases, in Erdmann Volker A., Markiewicz Wojciech T., Barciszewski Jan. (ed.), Springer, Berlin, Heidelberg, 75-94.
Dugovic Branislav, Wagner Michael, Leumann Christian J. (2014), Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bcen-T and iso-tricyclo-T nucleosides, in Beilstein Journal of Organic Chemistry
, 10, 1840-1847.
Hollenstein Marcel, Leumann Christian J. (2014), Synthesis and Biochemical Characterization of Tricyclothymidine Triphosphate (tc-TTP), in ChemBioChem
, 15, 1901-1904.
Smith Christine C., Hollenstein Marcel, Leumann Christian J. (2014), The synthesis and application of a diazirine-modified uridine analogue for investigating RNA-protein interactions, in RSC Advances
, 4, 48228-48235.
Roethlisberger Pascal, Wojciechowski Filip, Leumann Christian J. (2013), Enhancement of Excess Electron Transfer Efficiency in DNA Containing a Phenothiazine Donor and Multiple Stable Phenanthrenyl Base Pairs, in Chemistry – A European Journal
, 19, 11518-11521.
Stucki SilvanR, Désiron Camille, Nyakas Adrien, Marti Simon, Leumann ChristianJ, Schürch Stefan (2013), Gas-phase Dissociation of homo-DNA Oligonucleotides, in Journal of the American Society for Mass Spectrometry
, 24, 1997-2006.
Stoop Matthias, Désiron Camille, Leumann Christian J. (2013), Nucleic acid sensing by an orthogonal reporter system based on homo-DNA, in Artificial DNA: PNA & XNA
, 4, 28-33.
Evéquoz Damien, Leumann Christian Joerg, Probing the backbone topology of DNA: synthesis and properties of 7',5'-bicyclo-DNA, in Chemistry - A European Journal
This NF-grant application contains three separate sub-projects that all deal with the design, synthesis and the evaluation of novel, chemically modified oligonucleotide analogues. These analogues are of interest for DNA therapy, for DNA based functional materials and as tools to follow the cellular fate of base damaged RNA from a fundamental point of view.The first sub-project deals with the synthesis of novel nucleosides and oligonucleotide analogues of the bicyclo-DNA family with the aim of improving RNA affinity and cellular uptake and distribution. We will follow a combinatorial approach to screen a wide variety of backbone geometries in an efficient way. In addition we will apply the pro-drug concept to enhance membrane permeability of oligonucleotides. This research effort is devoted to improve the efficacy of current therapeutic oligonucleotides.The second sub-project is devoted to adding function to the phenanthrene DNA-zipper recognition motif that we discovered a few years ago. We will incorporate electronically differently substituted phenanthrene units into the center of a DNA duplex and will evaluate the electron transport properties through multiple phenanthrene units by using established electron injection methods as well as novel nanoelectrochemical methods in collaboration with the Wandlowski group in our department. We will particularly focus on the efficiency of electron transport as a function of the composition of electronically tuned phenanthrenyl units in the stack. The ultimate goal here is to construct an efficient charge separating device based on this novel DNA architecture.The last sub-project is concerned with the biological impact of base damaged RNA. Although the content of total RNA in a cell is >90% of all nucleic acids at any point in time, the biological consequences of RNA damage are absolutely underinvestigated in comparison to DNA. Having in hand a powerful method for the synthesis of a series of known base damaged oligoribonucleotides we plan to investigate the consequences of such RNA lesions on a model mRNA during translation at the ribosome in an in vitro translation assay. In addition, in collaboration with the Polacek group in our department, we will investigate the translation efficiency of ribosomes which show such lesions in their catalytic center. The results of this sub-project will increase our general understanding of the functional consequences of such RNA lesions.