Targeting of Nucleic Acids

Targeting of Nucleic Acids

Group leader: Maria DUCA

Research group new

RNA represents a major biological target for future drug development, because it is involved in a wide number of biological processes, such as transcription, translation or catalysis and more importantly it is essential for the regulation of gene expression. Most biologically relevant RNAs bear a three-dimensional structure containing single-stranded regions (loops and bulges) associated to double-stranded regions that offers the possibility for selective/specific binding interactions with proteins and small-molecule ligands. The main goal of our research activities is to design and synthesize new RNA ligands bearing both strong affinity and high selectivity for a biologically relevant RNA target and to study the interactions involved in the formation of the ligand-RNA complex using biochemical and biophysical techniques.

Do not hesitate to follow us on twitter @MariaDuca_CNRS for the latest news!

October 2020: Maria Duca is an invited speaker at MercachemSyncom conference Exploring new Modality Space by Precision Chemistry

September 2020: Review about smoll-molecule drugs inducing the differentiation of cancer stem cells published on ChemMedChem

August 2020: Review about aminoglycoside modification for RNA targeting now published in Chem. Eur. J. 

April 2020: New article published in Cancers

January 2020: New article published in ChemPlusChem

November 2019: Maria Duca is invited speaker at ICBS2019 to be held in Hyderabad (India) in November 2019 as well as at the symposium about Targeting RNA in Franckfurt (Germany).

October 2019: two new PhD students in the group, Maurinne BONNET and Mélanie PERNAK supported by MENRT and Sanofi, respectively

September 2019: Our new article is out in ChemCommun !

July 2019: New ANR-PRC grant obtained this year entitled "A new therapeutic target for ischemic-related injuries: application in organ transplantation" in collaboration with Michel TAUC at LP2M.

July 2019: Céline Martin won the best poster award at RICT2019 !

May 2019: Review about small-molecule RNA ligands accepted in MedChemComm !

April 2019: Oral communication accepted for European Chemical Biology Symposium in Madrid April 2019

January 2019: Welcome to Benjamin Zagiel (@BenjaminZagiel), we are very happy to have him in the group.



  • Maucort, C., Di Giorgio, A., Azoulay, S., Duca, M. Differentiation of cancer stem cells using synthetic small molecules: toward new therapeutic strategis against therapy resistance. ChemMedChem

  • Aradi, K., Di Giorgio, A., Duca, M. Aminoglycoside conjugation for RNA targeting: antimicrobials and beyond. Chem. Eur. J. 2020

  • Signetti, L., Elizarov, N., Simsir, M., Paquet, A., Douguet, D., Labbal, F., Debayle, D., Di Giorgio, A., Biou, V., Girard, C., Duca, M., Bretillon, L., Bertolotto, C., Verrier, B., Azoulay, S., Mus-Veteau, I. Inhibition of Patched Drug Efflux increases vemurafenib effectiveness against resistant BrafV600E melanoma. Cancers 2020 12, 1500.

  • Martin, C., De Piccoli, S., Gaysinski, M., Becquart, C., Azoulay, S., Di Giorgio, A., Duca, M. Unveiling RNA-binding Properties of Verapamil and Preparation of new derivatives as inhibitors of HIV-1 Tat-TAR interaction. ChemPlusChem 2020 85, 20.


  • Joly, J.P., Gaysinski, M., Zara, L., Duca, M., Benhida, R. Functionalized C-nucleosides as remarkable RNA binders: targeting of prokaryotic ribosomal A-site RNA. Chem. Commun. 2019 55, 10432.
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  • Vo, D.D., Becquart, C., Tran, T.P.A., Di Giorgio, A., Darfeuille, F., Staedel, C., Duca, M. Building of neomycin-nucleobase-aminoacid conjugates for the inhibition of oncogenic microRNAs biogenesis Org. Biomol. Chem. 2018 16, 6262.
  • Staedel, C., Tran, T.P.A., Giraud, J., Darfeuille, F., Di Giorgio, A., Tourasse, N.J., Salin, F., Uriac, P., Duca, M. Modulation of oncogenic miRNA biogenesis using functionalized polyamines Scientific Reports 2018 8, 1667.


  • Vo, D.D., Duca, M. Design of multimodal small molecules targeting miRNAs biogenesis : synthesis and in vitro evaluation Methods Mol. Biol.2017 1517, 137.
  • Duca, M. Interfering with Enzymatic steps of microRNAs pathway using small molecules in Advances in Studies on Enzyme Inhibitors as Drugs Ed. Novascience 2017 vol.1, p.83.


  • D.D. Vo, T.P.A. Tran, C. Staedel, R. Benhida, A. Di Giorgio, M. Duca Oncogenic microRNAs biogenesis as a drug target : structure-activity relationship studies on novel aminoglycoside conjugates Chem. Eur. J. 2016 22, 5350-5362.
  • A. Di Giorgio, T. P. A. Tran, M. Duca Small-molecule approaches toward the targeting of oncogenic microRNAs : roadmap for the discovery of RNA modulators, Future Med. Chem. 2016 8, 803-816.


  • T.P.A. Tran, D.D. Vo, A. Di Giorgio, M. Duca Ribosome-targeting antibiotics as inhibitors of oncogenic microRNAs biogenesis : Old scaffolds for new perspectives in RNA targeting. Bioorg. Med. Chem. 2015 23, 5334-5344
  • L. Pascale, A. López González, A. Di Giorgio, M. Gaysinski, J. Teixido Closa, R. Estrada Tejedor, S. Azoulay, N. Patino Deciphering structure-activity relationships in a series of Tat/TAR inhibitors. J. Biomol. Struct. Dyn. 2015


  • D.D. Vo, C. Staedel, L. Zehnacker, R. Benhida, F. Darfeuille, M. Duca Targeting the production of oncogenic microRNAs with multimodal synthetic small molecules. ACS Chem. Biol. 2014  9, 711-21.
  • J.P. Joly, G. Mata, P. Eldin, L. Briant, F. Fontaine-Vive, M. Duca, R. Benhida Artificial nucleobase-amino acid conjugates : a new class of TAR RNA binding agents. Chem Eur. J. 2014 20, 2071-9
  • Rocchi S., Ballotti R., Benhida R., Cerezo M., Duca M., Joly, J.P. Preparation of arylsulfonamido thiazole derivs. as antitumor agents PCT Int. Appl. (2014), WO 2014072486


  • L. Pascale, S. Azoulay, A. Di Giorgio, L. Zenacker, M. Gaysinski, P. Clayette, N. Patino (2013). Thermodynamic studies of a series of homologous HIV-1 TAR RNA ligands reveal that loose binders are stronger Tat competitors than tight ones. Nucleic Acids Res 11, 5851.
  • C.Y. Darini, P. Martin, S. Azoulay, M.D. Drici, P. Hofman, S. Obba, C. Dani, A. Ladoux (2013). Targeting cancer stem cells expressing an embryonic signature with anti-proteases to decrease their tumor potential. Cell Death Dis 4, E706


  • P. Vekhoff, M. Duca, D. Guianvarc’h, R. Benhida, P.B. Arimondo (2012). Sequence specific base pair mimics are efficient topoisomerase IB inhibitors. Biochemistry, 51, 43-51.
  • G. Upert, A. Di Giorgio, A. Upadhyay, D. Manvar, N. Pandey, V.N. Pandey, N. Patino (2012). Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop. J Nucleic Acids
  • V. Malnuit, M. Duca, R. Benhida (2011). Targeting DNA base pair mismatch with artificial nucleobases. Advances and perspectives in triple helix strategy. Org. Biomol. Chem., 9, 326-36.

We are an established research group that is focusing its activity on the design of new small-molecule ligands targeting biologically relevant RNAs that represent original and innovative therapeutic targets. All our projects aim at improving the fundamental understanding of selective interactions that could be formed between ligands and the target and at designing general rules for the rational design of selective RNA binders. These chemical tools are then applied to chemical biology and medicinal chemistry projects. 

Interrelated areas of focus include : 

1) Therapeutic innovations in antibiotics : focus on the targeting of toxin-antitoxin systems using small-molecule RNA binders

There is currently an urgent need for new antibiotics in order to overcome the steady emergence of multidrug-resistant bacteria and the associated human and economic cost. For the development of new antimicrobial agents, two major issues must be overcome : the difficulty to permeate bacterial membranes and the toxicity of compounds. Furthermore, the available number of specific targets remains restricted. All these issues led to a strong decrease in the efforts done toward the discovery of new antibiotics both in industry and in academia. In this context, the purpose of this project is the discovery of new antibiotics targeting original and so far unexploited targets : bacterial toxin-antitoxin (TA) systems. TA systems are small genetic elements composed of a toxin gene and its cognate antitoxin both coding for corresponding toxin and antitoxin products. The toxins of all known TA systems are proteins able to inhibit bacterial cell growth or lead to cell death, whereas the antitoxins are either proteins or small regulatory RNAs that neutralize the toxin. Here, we decided to target type I TA systems where the antitoxin is a non-coding RNA that binds to the messenger RNA (mRNA) coding for the toxin thus inhibiting its translation.

This project is performed in collaboration with Dr. Fabien Darfeuille at ARNA Laboratory in Bordeaux.                                                                  

This project is supported by ANR-PRC grant (ANR-PRC ANR-17-CE18-0009, 2018-2021).

2) Targeting oncogenic microRNAs: toward new chemotherapies

We have designed and synthesized various new series of RNA ligands able to bind selectively to two precursors of oncogenic microRNAs (pre-miR-372 and pre-miR-373) involved in the proliferation and tumorigenesis of gastric adenocarcinoma. The development of a cell-free high-throughput assay allowed the selection of most promising compounds for intracellular studies. We identified compounds able to selectively inhibit the production of oncogenic miRNAs and inhibit cancer cells proliferation and restor normal mRNA translation.

We also applied the HTS assay to the screening of larger libraries. As an example, the screening of the Essential Library belonging to the French National Chemical library led to the discovery of polyamine derivatives as promising compounds able to interfere with the biogenesis of oncogenic miRNAs.


3) A therapeutic target for ischemic related injuries: application in organ transplantation

 In intensive care units, clinicians have to fight against ischemia injury: a major issue encountered after organ transplantation that cannot be treated and that may lead to patient's death. The aim of this project is the preclinical development of new compounds targeting an innovative pathway that we have recently identified in mammals and whose inhibitors would be able to prevent the ischemia mediated tissular damages associated to the transplantation process.

This project is performed in collaboration with Dr. Michel TAUC at LP2M of Université Côte d'Azur and it is supported by ANR grant (ANR KIRI 2019-2021) 

4) Treating cancer as an infectious disease with antibiotics

Compelling evidence suggests that cancer stem cells (CSC) are the roots of current shortcomings in advanced and metastatic colorectal cancer treatment. CSC represents a minor subpopulation of tumor cells endowed with self-renewal and multi-lineage differentiation capacity which can escape from both conventional and targeted therapies (cetuximab, avastin), disseminate and seed metastasis. For that reason, Targeting CSC has become a major goal to design new therapeutic routes that may prevent tumor relapse and metastasis. Most drugs possess off-target effects that might provide substantial benefit for cancer treatment. Our recent work suggests that some antibiotics are able to interfere with stem-like properties -such as self-renewal- inherent to CSC phenotype. This project aims to determine whether these compounds can be used as adjuvant during the course of classic chemotherapy to target CSC and prevent disease recurrence and metastatic process.

The project is performed in collaboration with Dr. Alexandre DAVID at Institut de Génomique Fonctionnelle in Montpellier.

This work is supported by INCa grant (INCa PLBio 2017-160, 2018-2020) 

5) Targeting of viral RNAs : applications to HIV-TAR RNA

We prepared various glycoconjugates containing artificial nucleobases, sugars and amino acids in order to target the stem-loop structure of TAR RNA. This led to compounds bearing antiviral activity in infected cells upon inhibition of transcription.

6) Induction of cancer stem cells differentiation in glioblastoma using synthetic small molecules

Glioblastoma multiforme (GBM) is a lethal and therapy-resistant brain cancer comprised of several tumor cell subpopulations, including GBM stem-like cells (GSCs) which are believed to contribute to tumor initiation and to be responsible for recurrence following initial response to therapies. We discovered various hits among our library of RNA ligands that are able to induce GSCs differentiation and to increase their sensitivity to current chemotherapies by interfering with GSCs miRNAs network. The development of various series of analogs in order to improve the biological activity, describe structure-activity relationships and identify the molecular mechanism of action are currently in progress.

This project is performed in collaboration with Dr. Thierry Virolle at the Institut de Biologie Valrose.        

Each series of analogs is supported by different grants from ARC (Projet Fondation ARC 2017-2018) and SATTSud-Est (Maturation 2017-2021)



Group Leader

Maria Duca 

Permanent members 

Stéphane Azoulay (Assistant Professor) 
Audrey Di Giorgio (Assistant Professor) 
Nadia Patino (Full Professor) 

PhD Students

Chloé MAUCORT (2017-2020, Institut de Recherche Servier)
Sylvain POULET (2018-2021, IDEX UCA)

Céline MARTIN (2018-2021, ANR)
Mélanie PERNAK (2019-2022, CIFRE Sanofi)
Maurinne BONNET (2019-2022, MENRT)
Iryna SHCHEHOLEVA (2019-2022, COFUND)
Sandra KOVACHKA (2020-2023, COFUND)
Marc PANOSETTI (2020-2023, IIT)

Master Students

Former post-doctoral fellows and students

Alessandro MONTI, M2 (2020)
Benjamin ZAGIEL, Postdoc (2019-2020, INCa)
Samy AOUAD, M2 (2019, IDEX UCA)
Anaïs PAVEYRANNE, IE (2018-2019, CNRS).
Serena DE PICCOLI, MD (2017). Current position: PhD at ISIS (Strasbourg) 
Thi Phuong Anh TRAN, PhD (2013-2016). Current position: Lecturer at University of Nha Trang (Vietnam)
Dr. Duc Duy VO, Post-doc (2012-2014). Current position: Research Scientist at Uppsala University (Sweden) 
Jean-Patrick JOLY, PhD (2009-2013). Post-doc at Institut de Chimie Radicalaire of the University of Marseille 
Oleg Borodin, M2 (2016). Current position: PhD student in FAU Erlangen-Nuremberg (Germany)
Coralie CHARRAT, M2 (2012). 
Guillaume MATA, M2 (2012). Current position : after a PhD at ETH (Zurich), SNF Researcher at Stanford University.
Lorena ZARA, M2 (2013). Current position : PhD at Laboratoire ARNA (Bordeaux)
Anita RAYAR (post-doc 2017-2018). Current position: Laboratoires Servier
Klara ARADI (post-doc 2018).
Alexandra Gresika (2016-2018). Current position: Novalix

Why Nice

Université Côte d’Azur among the 10 main French universities 

The Université Côte d’Azur (UCA) is a community of universities and institutions (COMUE) which, in addition to its 13 members, groups together public and private entities of higher education and research. In 2016, UCA was awarded the very selective "IDEX" Future Investment Program with the UCAJedi (Joint, Excellent & Dynamic Initiative) project aimed at identifying the top 10 French universities. The investment of nearly 600 million euros that will be allocated to UCA will generate 14.5 million euros per year.

The Institute of Chemistry of Nice belongs to Université Côte d’Azur and includes four main research axes :

  • Bioactive Molecules
  • Fragrances : synthesis and molecular modeling
  • Human and Environmental Radiochemistry
  • Sustainable materials and polymers

TNA research group belongs to the Bioactive Molecules axes. 

Living in Nice 

Capital of the French Riviera, Nice enables quick and easy access to the entire coastline as well as the mountain resorts and the Mercantour National Park, only 1.5 hours from the sea. In this natural environment, every season is conducive to incentives, unusual itineraries, and adventures. Nice enjoys an exceptional microclimate which contributes to its eminence, with more than 300 days of sunny days.

Located in the heart of the city, just 15 minutes from the Airport (2ⁿd International airport in France), Sciences Campus includes chemistry, biology and physics institutes together with mathematics, informatics and geology.

Positions available

PhD Fellowships

Funding opportunities are regularly available for PhD students. Candidates should forward a CV and contact information to

Master’s Projects 

Highly motivated candidates should send their CV and a transcript of their marks to in summer-fall 2020 for a project starting in early 2021.