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How to make valuable molecular tools to study G4 biology? The answer is in Chem. Eur. J.!

[Nov. 13, 2025] I would like to thank the editorial team of Chem. Eur. J. for inviting me to contribute to the special issue dedicated to Prof. Seela. We seized this opportunity to describe a new synthetic scheme we developed to access TASQs in a far more straightforward and versatile manner. This so-called 'convergent' synthesis, which enables the ready preparation of different multivalent TASQs, relies on the chemistry of AMC (aminomethylcyclene). Despite its apparent simplicity, working with AMC remains challenging and intricate! Our work is now fully detailed in Chem. Eur. J. A special thank you to Sandy for her dedication and hard work!

A first article dealing with CRISPR devices now in Analytical Chemistry

[Oct. 30, 2025] Another type of biotechnological applications for G4s: in this novel Anal. Chem. article, G4s were used for controlling the activity of a CRISPR-Cas12a device in a spatio-temporal manner, this system being aimed at diagnosing viral infection (human papilloma virus, HPV). Indeed, the size and shape of G4s make them ideal blocks to impede access to the CRISPR RNA, thereby annihilating the device’s activity. Upon photo-activation, the trigger is removed and the activity of the device restored, making it able to cleave HPV DNA in small fragments, which then hybridize with fluorescently labelled synthetic oligonucleotides to provide readily monitored (and highly sensitive) fluorescence readout. And it works quite well! Thank you, Jun and his team!

A novel article in Natl. Sci. Rev.

[Oct. 21, 2025] DNA catalysts are studied for decades, and new applications are reported almost on a daily basis. This is particularly true for DNA G4 catalysts, or G4-DNAzymes. While hundreds of applications have been developed so far, only a few of them have been shown to be implementable in real-life conditions. Thanks to a series of nature-inspired optimizations of the active center of a G4-hemin-peptide conjugate, it was possible to endow the resulting G4-DNAzyme with both peroxidase (POD) and catalase (CAT) activity: the resulting system, referred to as bi-CPDzyme, was used for remediation of real industrial wastewater samples (printing and dyeing industry), where its POD activity was useful to degrade polluting dyes and its CAT activity to remove the oxidizing agent. Now accepted for publication in Natl. Sci. Rev., the journal of the Chinese Academy of Sciences (IF >17!): thrilling!

New TASQ (photoMultiTASQ) = new article!

[Sep. 30, 2025] We are happy to report in ACS Bio & Med Chem Au the synthesis and in vitro validations of our brand new TASQ named photoMultiTASQ, which is both photoactivatable and clickable. This TASQ is a new molecular tool in the arsenal of chemical cross-linking and isolation by pull-down (Chem-CLIP) technologies, which could lead to the identification of both G4 targets and associated proteins (G4BPs) in cells. A beautiful collaboration with the teams of Oscar (IPHC Strasbourg, FR) and Eran (WIS Rehovot, IS), supported by CNRS MITI. 

Stanford's list of top-cited scientists (for 2024)

[Sep. 23, 2025] Quite honored to appear in this prestigious list for the fifth year in a row (here). It does not mean much in terms of science per se but I am just thrilled to be there, which is some sort of peer recognition of the determination and tireless work done by my team and colleagues in a not-often-easy national and international context. Thanks to all of them!

An interview in Pour La Science

[Aug. 17, 2025] Earlier this year, Knipscheer et al. published an interesting paper in Science in which they described how cells could use G-loops to resolve G4s and alleviate G4-mediated genetic instability. I was invited to discuss these findings in the 'generalist' science magazine Pour La Science. You can read the article here (sorry, it's only available in French).

A novel article in Analytical Chemistry

[July 24, 2025] In this work, we establish a novel label-free, DNA-based system used for the specific and sensitive detection of colistin, an antibiotic that is widely used nowadays notably in animal husbandry, which is found as health-threatening pollutant in groundwater. Using a G4-based system we developed a device able to detect colistin with a limit as low as 0.4 ng/mL through a color change (luminol oxidation) and assessed this easy-to-implement method under real conditions (milk samples). Now published in Anal. Chem. Thank you Jun and co-workers!

A novel article in BMC Biology

[July 04, 2025] In this study, now published in BMC Biol., we investigated the G4-forming sequences found in three long non-coding RNAs (lncRNAs) known to be dysregulated in colorectal cancer (CRC), i.e., LINC01589, MELTF-AS1 and UXT-AS1. We applied a pure chemical biology approach in which we positively and negatively modulate these G4s using ad hoc molecular tools, i.e., the G4 stabilizer BRACO-19 and the G4 destabilizer PhpC, and assessed the cellular outcomes of this modulation. This led us to describe a fully innovative anticancer strategy, disturbing the homeostasis and inner functioning of CRC lncRNAs. Now published in BMC Biol. as a part of the “Regulation of gene expression through RNA” Collection, Guest Edited by Marco Mangone and Gian Gaetano Tartaglia. Thanks to Shubham and Bhaskar (IIT Gandhinagar, India) for this collaborative work, and EMBO for funding the Shubham's internship in Dijon.

A novel article in Int. J. Biol. Macromol.

[June 18, 2025] For several years now, we aim at demonstrating that PhpC can be used as a molecular helicase prone to unfold both DNA and RNA G4s in cells. Thanks to a collaboration with Carla Cruz, we now provide another demonstration of this activity, showing that PhpC does indeed unfold RNA G4s belonging to pre-miRNA in cells quite efficiently. To this end, a series of biophysical techniques was implemented (notably an NMR titration that was attempted for the very first time with this molecule) along with a series of cell-based assays, which shows both the decrease in G4 abundance and the modification of that of the corresponding miRNA (miR-3196) upon PhpC incubation. These results thus provide another demonstration of the promising helicase-mimicking properties of PhpC ; they are now accepted for publication in Int. J. Biol. Macromol. Many thanks to Carla and her collaborators for this beautiful work.

IMAJ#1: what a beautiful meeting!

[May 15, 2025] It was an absolute pleasure to organize the 1st International Meeting on Nucleic Acid Junctions (IMAJ#1) in Paris from May 12 to 14, 2025. This meeting was supported by the CNRS as part of the creation of an International Research Network (IRN), bringing together EU researchers from the UK, Spain, Ireland, and France. I had the opportunity to meet friends and colleagues, and colleagues who quickly became friends. The event featured three days of excellent talks, lively discussions, and enriching exchanges. Many thanks to all and stayed tuned, we will start again next year!

ScholarGPS's list of top scholars (for 2024)

[May 01, 2025] I am quite happy to appear on the ScholarGPS list of top scholars worldwide (here). Admittedly, this does not mean much in terms of science per se, but I am thrilled to be included, especially as the list is compiled in a way that excludes self-citations and combines quantity and quality, thus removing some biases... :-) 

A novel article in Nature Communications

[Mar. 13, 2025] The aim of this study is to better understand how mitochondrial metabolism can affect cancer development. The synthesis of mitochondrial proteins occurs in the cytoplasm, and more precisely at the outer mitochondrial membrane, where the hnRNP U binds to RNA, and particularly G4-containing RNA, and cooperates with the helicase DDX3X to unwind G4s that may fold within mitochondrial RNA and hamper proper translation. If these G4-forming sequences are stabilized by ligands (eg, PhenDC3), then their translation is downregulated, which eventually inhibits mitochondrial respiration and functions, thereby jeopardizing the fate of cancer cells. This strategy, which is currently actively studied to fight against cancers, is fully validated herein. This manuscript is now accepted for publication in Nat. Commun.: many thanks to Stefania and her team for their pugnacity and dedication!

A novel article in the J. Am. Chem. Soc. (JACS #10!)

[Feb. 19, 2025] Gaining insights into the existence, prevalence and functional relevance of RNA G4s relies on efficient but technically challenging methods such as rG4-seq (in vitro) or G4RP-seq (in vivo). The latter technique involved a G4-RNA-specific precipitation (or G4RP) using biomimetic ligands (TASQs) as molecular baits, before affinity-based separation (biotin/streptavidin) and identification (sequencing) steps. Quite efficient (see our Nat. Protoc. and STAR Protoc.) but how to simplify this? By merging precipitation and separation steps. How? By exploiting the quite unique G4-interacting properties of colistin (COL), which interacts with and precipitates RNA G4 only. The resulting technique, named CoRP-seq, allows for identifying RNA G4s at a transcriptome-wide scale in a faster, simpler manner. Thrilling! Now published in the J. Am. Chem. Soc.: Thank you Jun and his team for this huge work!

A new protocol for in situ click G4 imaging now in bio-protocol

[Jan. 22, 2025] Angie has invested massive efforts to be as specific as possible in describing how to detect G4s in human cells using our clickable TASQs (notably the commercially available MultiTASQ). The protocol, which is now freely available here, provides you with all necessary details and wet lab tips and tricks to successfully, reliably and reproducibly track DNA and RNA G4s, in live or fixed cells. Thanks Angie for this huge work! 

ChemMedChem - Special Collection "Drug Discovery in France" 

[Dec. 20, 2024] Happy to end this year with an invited article now published in ChemMedChem, which supports the Société de Chimie Thérapeutique (SCT) through the Special Collection "Drug Discovery in France" edited by Rebecca Deprez-Poulain (University of Lille), Maria Duca (University of Côte d'Azur) and Gilles Guichard (University of Bordeaux). We thus took this opportunity to describe a series of investigations carried out in collaboration with Petra Menova (University of Chemistry and Technology, Prague, CZ), Gabor Paragi (Institute of Physics, University of Pécs, HU; Department of Theoretical Physics, University of Szeged, HU) and Nicolas Chéron (PASTEUR, Département de chimie, ENS Paris, FR). We aimed at uncovering the mechanism behind the exquisite photophysical properties of N-TASQ, a twice-as-smart G4 probe that allows for tracking RNA G4s in live cells. We reported on the synthesis and in vitro studies of AlkN-TASQ and TzN-TASQ, which provides very interesting insights into the way through which N-TASQ derivatives label G4s. Thrilling!

The new version of the G4RP (G4-RNA-specific precipitation) protocol now in STAR Protocols

[Dec. 11, 2024] Jérémie spent the last months (to say the least :-)) to make the G4RP protocol fully reliable and reproducible. To this end, each step of the 1st version (published in Nat. Commun. in 2018, and in Nat. Protoc. in 2022) developped with Judy and Sunny was optimized, and he added a series of control and go/no-go steps. This new version, G4RP.v2 is now published in STAR Protocols:  more than 40 steps, over more than 40 pages, impossible not to be succesful now! Congrats Jérem!

A new article in J. Biol. Chem.

[Nov. 29, 2024] Certainly one of the ones I am most proud of. In this J. Biol. Chem. article, we carried out a real chemical biology investigation in which we positively and negatively modulate the G4 landscape in patient-derived human astrocytes, using the G4 ligand PDS and the molecular helicase PhpC, respectively. This allowed us for assessing the cellular consequences at both transcription and translation levels by RNA-seq and proteomics, respectively, and drawing a series of conclusions concerning 1/ the actual regulatory roles of G4s, and 2/ the actual influence of both molecular tools in human cells. A long-term and absolutely thrilling scientific adventure.. congrats to all co-authors!

An interview by the CNRS (podcast)

[Oct. 24, 2024] Extremely honored to have been interviewed by the CNRS to freely speak about G4s, my feelings and thoughts about the G4-focused research, the achievements and futur challenges, notably in the field of age-related diseases. Part of the interview (text) here: https://www.centre-est.cnrs.fr/fr/lumiere-sur-les-quadruplexes-dadn; the complete interview (audio, 25 min) here: https://youtu.be/NbVgqAKaRsg?list=PLWbM_xdKU4muTdpg5JA5OSemiL72XXI-Q (sorry, only in French)

Our Angew. Chem. Int. Ed. article highlighted by the CNRS

[Oct. 15, 2024] Quite happy that the CNRS decided to highlight the results we recently published in Angew. Chem. Int. Ed. in which we showed that three-way DNA junctions (TWJs) are promising targets for anticancer therapeutic intervention and that azacryptands are specific TWJ ligands, meaning promising anticancer agents. The highlight can be found here (sorry, only in French)

A novel article in Nucleic Acids Res.

[Sep. 17, 2024] Thank you so much Sara (Sara Richter, University of Padua, IT) for associating me to a beautiful study aiming at understanding the molecular basis of X-linked dystonia Parkinsonism (XDP). This study, now published in Nucleic Acids Res. aims at understaning the role that G4s play in the regulation of the expression of TAF1 gene (dysregulated in XDP), and how it is possible to modulate its expression using our G4 unfolder PhpC. A small contribution to a brilliant and thrilling study! 

Stanford's list of top-cited scientists (for 2023)

[Sep. 16, 2024] Quite honored to appear in this prestigious list for the fourth year in a row (https://dx.doi.org/10.17632/btchxktzyw.7). It does not mean much in terms of science per se but I am just thrilled to be there, which is some sort of peer recognition of the determination and tireless work done by my team and colleagues in a not-often-easy national and international context. Thanks to all of them!

A tribute to the contribution of Stephen Neidle to the field of G4 ligands

[Sep. 7, 2024] It was an honor for me to be invited to contribute to a special issue of Med. Chem. Res. honoring Prof. Stephen Neidle: I took this opportunity to retrace his carreer and highlights his most significant contributions to the field, from the publication of the very first G4 ligand in 1997 to the recent clinical investigations of his latest ligand QN302.  This contribution is a personnal view on this fascinating scientific story (might be biased, admittedly) but I really enjoyed writing it!

A novel article in Analytical Chemistry

[Aug. 21, 2024] In the framework of our ongoing (and long-lasting) collaboration with Jun Zhou (Nanjing U., PRC), we keep on investigating the power of G4-based catalysis. In this novel Anal. Chem. article, we chemically modified the cofactor hemin to recreate (somehow) its binding site within its natural proteinic partner HRP to increase the catalytic efficiency of the G4/hemin complex. The validity of this apporach was confirmed through the development of a colorimetric assay for the detection of FEN1 enzyme.  

Thanks to the ANR for supporting our Top2G4 project

[July 04, 2024] We are quite happy that our Top2G4 project ("understanding and tuning the cellular properties of G4 ligands") has been funded by the ANR. This project is steered by Sébastion Britton (IPBS Toulouse, FR), in collaboration with Valerie lamour (IGBMC Strasbourg, FR). We will investigate the mechanism(s) behind the cellular properties of G4 ligands in the aim of rationalizing the differences between standards in the filed (PDS, PhenDC3, CX5461, etc.). Thanks Sébastien for your efforts in gathering this wonderful consortium and desiging this beautiful project!

A novel article in Angew. Chem. Int. Ed.

[June 25, 2024] In this Angew. Chem. article, we not only describe an array of highly promising ligands for three-way DNA junctions (TWJs) from the azacryptand series but also a panel of techniques to investigate their TWJ-interacting properties in vitro but also their ability to stall DNA transactions, therefore moving closed to predictive models for cellular investigations. Another great collaboration with my 'TWJ dream team'': Anton Granzhan (Curie Orsay, FR), Sébastien Britton (IPBS Toulouse, FR), Nicolas Chéron (Pasteur Paris, FR) and Lukas Trantirek (CEITEC, CZ).

An article in Advanced Science

[June 25, 2024] In this article now published in Adv. Sci., we report on a supramolecular nanomaterial (referred to as AA-heminzyme) which is prepared in a straightforward manner (a kind of mix-and-measure approach) and is used for performing catalytic oxidation reactions. Its practical use was demonstrated by the smartphone-based detection of a circulating cancer biomarker.. thrilling! Another great collaboration with Dr. Jun Zhou (Nanjing U. PRC).

Thanks to CNRS Chimie for supporting the creation of an International Research Network (IRN)

[June 21, 2024] The time is ripe to gather the community of researchers working on DNA junctions under a single banner... and CNRS Chimie gives us this possibility! Thanks to quite interesting discussions with Mike Hannon and Mark Searcey (Birmingham and Norwich UK) on one side, and Miguel Vazquez Lopez and Eugenio Vazquez  (Santiago di Compostela, ES), we are poised to create an IRN on DNA and RNA junctions in order to 1/ optimize the connection between the different European partners on the basis of the complementarity of their expertise, 2/ secure an optimized scientific workflow between them from chemistry to biology, through in silico and structural studies, and 3/ coordinate this research effort thanks to a dedicated budget used for organizing workshops, student exchange and visiting professorship programs.   

An review in Trends in Genetics on i-motifs

[June 19, 2024] An i-motif (iM) is a four-stranded (quadruplex) DNA/RNA structure that folds from cytosine (C)-rich sequences. These peculiar structures are thought to play key roles in various DNA transactions but which ones?? In this review now published in Trends Genet., we sum up the techniques applied to assess the folding of iMs in vitro and the factors that affect their formation and stability in vivo in a comprehensive manner. A great collaboration with Dr. Wenli Zhang (Nanjing U. PRC).

Thanks to CNRS Innovation for funding the MoBiDiC project

[June 06, 2024] We would like to sincerely thank CNRS innovation for funding the MoBiDic project (for Molecular, Biomimetic probes for the Diagnosis of Cancers) which will also us to keep on developing new TASQs for whole-body applications (small animals). These new investigations will thus provide us with the opportunity to expand our TASQ portfolio for new applications in oncology (nuclear imaging).

Congrats to Garance for securing her PhD in the lab!

[May 27, 2024] We are really happy to announce that Garance Psalmon, currently in M2 internship in the lab, has successfully passed a quite challenging examination to obtain a PhD grant (funded by the Conseil Regional de Bourgogne, CRB) for the next 3 years in the GATTACA Lab. She will work on the biology of DNA and RNA G4s, modulating their formation in cells using both stabilizers and destabilizers. Very happy to have her in the lab for 3 more years!   

Promoted

[March 12, 2024] It is a huge honour to have been promoted to the rank of CNRS Research Director 1st class (I am therefore a quite old researcher by now, and officially :-)). Of course, without would have been possible without talented students and wonderful collaborators. Many thanks to all of them!

Two new bioRxiv preprints now available 

[Feb. 21, 2024] Quite happy to be associated to a beautiful study steered by Stefania Millevoi (CRCT Toulouse, FR) that shows how RNA G-quadruplexes (G4s) regulate mitochondrial mRNA translation and how G4 ligands modulate mitochondrial functions in cancer cells, thus providing a functional link between G4s and energy metabolism. Now available here: https://www.biorxiv.org/content/10.1101/2024.01.29.577192v1. And quite happy too to collaborate once more with Andrey S. Tsvetkov (UTHealth, Houston, TX USA) to perform a study in the best traditions of chemical biology in which we either positively (or stabilize) or negatively regulate (or destabilize) G4s in human astrocytes in order to gain insights into the prevalence of G4-mediated cellular circuitries in brain cells. Now available here: https://www.biorxiv.org/content/10.1101/2024.02.16.580621v1. 

Our ChemComm article highlighted by the CNRS 

[Jan. 23, 2024] Quite honored and proud to have been interviewed by the CNRS about the results we recently reported in ChemComm. The question was about the potential application of these discoveries, which are quite huge for both fundamental and applied research. We discussed about G-quadruplex-DNA (quite unsurprisingly) but also cancers, aging and to potential use of our prototype of G4 destabilizer PhpC (see the original article here). The article can be found here, the interview here (sorry, only in French)