NUCLEIC ACIDS CHEMISTRY
Group Leader: Ramon Eritja
The synthesis of nucleic acids (DNA and RNA) is in constant evolution providing a wide range of versatile tools with applications in therapeutics, and material science. Our studies are aimed at gaining a better understanding of novel nucleic acids by chemical modification with the objective of evaluating their efficacy in antisense and RNA interference therapies. The projects undertaken by the group deals with the structural properties of nucleic acids in particular with the introduction of modified nucleotides or conjugates. In addition, we have undertaken the synthesis of new transfecting agents based on cationic lipids for the improvement of nucleic acids delivery. Finally, we develop nucleic acid molecules designed for the assembly of nanomaterials and biosensor systems for detecting biologically relevant DNA and RNA molecules.
Non-canonical structures and nucleic acids conjugates
- Triplex: chemical modifications and structural stability studies
- G-Quadruplex: chemical modifications in loops and tetrads, new architectures, design of specific ligands of biologically relevance sequences
- i-Motif: physico-chemical characterization, design of specific ligands of biologically relevance sequences, quantitative evaluation of duplex/i-motif formation
- Nucleic acids conjugates: lipids, carbohydrates, intercalating agents, peptides/PNA, dyes, polymers
- Oligonucleotides with non-natural nucleosides with structural and biological relevance
Therapeutic oligonucleotides
- small interfering RNA, siRNA: improve stability, gene silencing efficacy and selectivity (reduce off-target effects); structural characterization of siRNA-protein interaction; delivery systems
- Antisense DNA: modulate nuclease stability; delivery systems using new transfecting agents
- microRNA: miRNA mimetics and inhibitors (antagomirs)
- Aptamers: enhance lifetime stability; cytotoxic drug carriers
DNA nanotechnology (biomedical and bio-sensing applications)
- DNA-template assembly of nanoscale architectures (rectangle DNA origami, DNA tetrahedron)
- DNA nanoscaffolds: Biosensors for DNA repair and thrombin detection; delivery systems for cytotoxic drugs, lithography templates for patterning gold surfaces
- DNA-based probes for miRNA and DNA methylation detection
Scientific staff
Ramon Eritja
Research Professor
ramon.eritja@iqac.csic.es
Lab people
Ana Mª Aviñó
CIBER Researcher
ana.avinyo@iqac.csic.es
Mª Carme Fàbrega
Postdoctoral Researcher
carme.fabrega@iqac.csic.es
Santiago Grijalvo
CIBER Researcher
santiago.grijalvo@iqac.csic.es
Andreia Fernandes
Postdoctoral Researcher
andreia.fernandes@iqac.csic.es
- Selective depletion of metastatic stem cells as therapy for human colorectal cancer-
Céspedes, M.V., Unzueta, U., Aviñó, A., Gallardo, A., Álamo, P., Sala, R., Sánchez-Chardi, A., Casanova, I., Mangues, M.A., Lopez-Pousa, A., Eritja, R., Villaverde, A., Vázquez, E., Mangues, R.
EMBO Molecular Medicine, 10 (10), art. no. e8772, 2018
- Design of oligonucleotide-capped mesoporous silica nanoparticles for the detection of miRNA-145 by duplex and triplex formation-
Ribes, À., Santiago-Felipe, S., Aviñó, A., Candela-Noguera, V., Eritja, R., Sancenón, F.,Martínez-Máñez, R., Aznar, E.
Sensors and Actuators, B: Chemical, 277, pp. 598-603. 2018
- Naturally occurring quaternary benzo[: C] phenanthridine alkaloids selectively stabilize G-quadruplexes-
Jarosova, P., Paroulek, P., Rajecky, M., Rajecka, V., Taborska, E., Eritja, R., Aviñó, A., Mazzini, S., Gargallo, R., Taborsky, P.
Physical Chemistry Chemical Physics, 20 (33), pp. 21772-21782.2018
- The influence of the polar head-group of synthetic cationic lipids on the transfection efficiency mediated by niosomes in rat retina and brain-
Ojeda, E., Puras, G., Agirre, M., Zarate, J., Grijalvo, S., Eritja, R., Martínez-Navarrete, G., Soto-Sánchez, C., Diaz-Tahoces, A., Aviles-Trigueros, M., Fernández, E., Pedraz, J.L.
Biomaterials, 77, 267-279 (2016).
- Oligonucleotide delivery: a patent review (2010-2013)-
Grijalvo, S., Aviñó, A., Eritja, R.
Expt. Opin. Ther. Patents, 24(7), 801-819 (2014).
- Quadruplex nanostructures of d(TGGGGT): influence of sodium and potassium ions Pontinha, A.D., Chiorcea-Paquim, A.M., Eritja, R., Oliveira-Brett, A.M.-
Anal. Chem., 86(12), 5851-5857 (2014).
- Cationic vesicles based on non-ionic surfactant and synthetic aminolipids mediate delivery of antisense oligonucleotides into mammalian cells-
Grijalvo, S., Alagia, A., Puras, G., Zarate, J., Pedraz, J.L., Eritja, R.
Coll. Surf. B: Biointerfaces, 119, 30-37 (2014).
- A novel cationic niosome formulation for gene delivery to the retina-
Puras, G., Mashal, M., Zárate, J., Agirre, M., Ojeda, E., Grijalvo, S., Eritja, R., Díaz-Tahoces, A., Martínez Navarette, G., Avilés-Trigueros, M., Fernández, E., Pedraz, J.L.
Control. Rel., 174(1), 27-36 (2014).
- Solution equilibria of cytosine- and guanine-rich sequences near the promoter region of the n-myc gene that contain stable hairpins within lateral loops-
Benabou, S., Ferreira, R., Aviñó, A., González, C., Lyonnais, S., Solà, M., Eritja, R., Jaumot, J., Gargallo, R.
Biochim. Biophys. Acta (General subjects), 1840, 41-52 (2014).
- siRNA Modified with 2'-Deoxy-2'-C-methylpyrimidine Nucleosides-
Dellafiore, M., Aviñó, A., Alagia, A., Montserrat, J.M., Iribarren, A.M., Eritja, R.ChemBioChem, 19(13):1409-1413 (2018).
- Evaluation of the effect of polymorphism on G-quadruplex-ligand interaction by means of spectroscopic and chromatographic techniques-
Benito, S., Ferrer, A., Benabou, S., Aviñó, A., Eritja, R., Gargallo, R.Spectrochim Acta A Mol Biomol Spectrosc, 196, pp. 185-195 (2018).
- DNA-based nanoscaffolds as vehicles for 5-fluoro-2’-deoxyuridine oligomers in colorectal cancer therapy-
Jorge, A.F., Aviñó, A., Pais, A.A.C.C., Eritja, R., Fàbrega, C.
Nanoscale 2018, 10(15), 7238-7249.
- Glucose-nucleobase pairs within DNA: impact of hydrophobicity, alternative linking unit and DNA polymerase nucleotide insertion studies-
Vengut-Climent, E., Peñalver, P., Lucas, R., Gómez-Pinto, I., Aviñó, A., Muro-Pastor, A., Galbis, E., de Paz, V., Fonseca Guerra, C., Bickelhaupt, M., Eritja, R., González, C., Morales, J.C.
Chem. Sci. 2018, 9, 3544-3554 .
- Stem-cell based gene delivery mediated by cationic niosomes for bone regeneration purposes.-
Attia, N., Mashal, M., Grijalvo, S., Eritja, R., Zárate, J., Puras, G., Pedraz, J.L.
Nanomedicine: Nanotechnology, Biology, and Medicine 2018, 14(2), 521-531.
- Isosteric Substitution of 4 H-1,2,4-Triazole by 1 H-1,2,3-Triazole in Isophthalic Derivative Enabled Hydrogel Formation for Controlled Drug Delivery-
Häring, M., Rodríguez-López, J., Grijalvo, S., Tautz, M., Eritja, R., Martín, V.S., Díaz Díaz, D.
Molec Pharm (2018), 15 (8), 2963-2972.
- Covalent strategies for targeting messenger and non-coding RNAs: An updated review on siRNA, miRNA and antimiR conjugates-
Grijalvo, S., Alagia, A., Jorge, A.F., Eritja, R.Genes, 9 (2), art. no. 74, (2018).
- Exploring PAZ/3’-overhang interaction to improve siRNA specificity. A combined experimental and modeling study.-
Alagia, A., Jorge, A.F., Aviño, A., Cova, T.F.G.G., Crehuet, R., Grijalvo, S., Alberto Pais, A.A.C.C., Eritja, R.
Chem. Sci. 2018, 9, 2074-2086.
- Cationic nioplexes-in-polysaccharide-based hydrogels as versatile biodegradable hybrid materials to deliver nucleic acids.-
Grijalvo, S., Alagia, A., Puras, G., Zárate, J., Mayr, J., Pedraz, J. L., Eritja, R., Díaz Díaz, D.
Mat. Chem. B, 2017, 5, 7756-7767
- Boronic acid-modified alginate enables direct formation of injectable, self-healing and multistimuli-responsive hydrogel-
Pettignano, A., Grijalvo, S., Häring, M., Eritja, R., Tanchoux, N., Quignard, F., Díaz Díaz, D.
Chem. Commm. 2017, 53(23), 3350-3353.
- Oligonucleotide-lipid conjugates forming G-quadruplex structures are potent and pangenotypic hepatitis C virus entry inhibitors in vitro and ex vivo-
Koutsoudakis, G., Paris de León, A., Herrera, C., Dorner, M., Pérez-Vilaró, G., Lyonnais, S., Grijalvo, S., Eritja, R., Meyerhans, A., Mirambeau, G., Díez, J.
Antimicrob. Agents Chemother. 2017, 61(5), e02354-16.
- DNA-origami-driven lithography for patterning on gold surfaces with sub-10 nanometer resolution-
Gállego, I., Manning, B., Prades, J.D., Mir, M., Samitier, J., Eritja, R.
Adv. Mat. 2017, 29(11), 1603233.
- The effect of L-thymidine, acyclic thymine and 8-bromoguanine on the stability of model G-quadruplex structures-
Aviñó, A., Mazzini, S., Fàbrega, C., Peñalver, P; Gargallo, R.; Morales, J. C., Eritja, R.
Biochim. Biophys. Acta (General Subjects) 2017, 1861, 1205-1212.
- Controlling the reversible assembly of liposomes through a multi-stimuli responsive anchored DNA-
Hernández-Ainsa, S., Ricci, M., Hilton, L., Aviñó, A., Eritja, R., Keyser, U. F.
Nano Lett. 2016, 16(7), 4462-4466 .
- Glucose-nucleobase pseudo base pairs as a new biomolecular interaction in a DNA context-
Vengut-Climent, E., Gómez-Pinto, I., Lucas, R., Peñalver, P., Aviñó, A., Fonseca-Guerra, C, Bickelhaupt, F.M.., Eritja, R., González, C., Morales, J.C.
Angew. Chem. Int. Ed. Engl., 55(30), 8643-8647 (2016).
- siRNA and RNAi optimization-
Alagia, A., Eritja, R.
WIREs RNA, 7(3), 316-29 (2016).
- Label-free electrochemical DNA sensor using click-functionalized PEDOT electrodes.-
Application to Hepatitis C virus detection
Galán, T., Prieto, B., Alvira, M., Eritja, R., Götz, G., Bäuerle. P., Samitier, J.
Biosens. Bioelectron., 74(1), 751-756 (2015).
- Direct covalent attachment of DNA microarrays by rapid thiol-ene Click chemistry.-
Escorihuela, J., Bañuls, M.J., Grijalvo, S., Eritja, R., Puchades, R., Maquieira, A.
Bioconjugate Chem., 25(3), 618-627 (2014).
