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Two great scientists and excellent people pioneers on Nucleic Acids Chemistry

Nucleic Acid Chemistry is an interdisciplinary discipline that combines organic chemistry, biochemistry, pharmacology, materials chemistry and biophysics. It started soon after the Watson–Crick model of DNA with the synthesis of the first dinucleotide, published in 1955. However, in the last decade, this field has blossomed, with the demonstration that Nucleic Acid Chemistry can provide innovative solutions to health problems such as vaccination, pathogen detection, and the treatment of metabolic or genetic diseases as well as providing important tools for the interrogation of cellular mechanisms.

Profesor Ramon Eritja, Scientific director of the Oligonucleotides Synthesis Platform U29 from ICTS NANBIOSIS will chair next January 13 a webinar on Frontiers in Nucleic Acid Chemistry, organized by the Journal Molecules in which some examples of the recent developments in Nucleic Acid Chemistry will be explained.

This webinar is dedicated to the memory of Prof. Enrique Pedroso one of pioneering researchers and leading Spanish scientist in Oligonucleotide and Peptide Synthesis who passed away in September of 2020. His contributions on the synthesis of modified oligonucleotides and especially oligonucleotide conjugates and cyclic oligonucleotides have opened new avenues in the search for novel applications of oligonucleotides. In addition, Enrique was deeply involved in the research and promotion of nucleic acid chemistry, as an active member of the IRT Society as well as organizing the Spanish Nucleosides Nucleotides and Nucleic Acids meetings (RANN).

During the preparation of the webinar we received the sad news of the decease of Prof. Ned Seeman from New York University who pioneered the field of DNA nanobiotechnology demonstrating that DNA is an excellent tool for the assembly of complex two and three-dimensional DNA lattices with important applications in several fields. 

We remained sad for the loss of these great scientists and excellent persons. 

Program and free registry for the webinar here

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A potential solution to decrease toxicity in colorectal cancer treatment

Cancer is one of the world’s leading causes of death, with over 18.1 million cases and 9.6 million deaths in 2018. One of the most successful drugs used in chemotherapy for the treatment of diverse severe cancers is 5-Fluorouracil (5-FU), however, one of the major problems described in clinical practice is 5-FU cell resistance.

Resarchers of the Nucleic Acids group and the Colloidal and interfacial Chemistry Group of CIBER-BBN at IQAC-CSIC have collaborated in a research to  inspect and test the ability of parallel G-quadruplexes to deliver floxuridine oligonucleotides into different types of cancer cells; finally, the internalization ability and the antiproliferative action of these oligoFdU-G-quadruplexes have been evaluated in FU-resistant cell lines.

Recently an article has been published with the research results by the Jorunal of Molecules entitled “Parallel G-quadruplex structures increase cellular uptake and cytotoxicity of 5-Fluoro-2′-deoxyuridine Oligomers in 5-Fluorouracil resistant cells”

The article describes a potential solution to decrease the toxicity of floxuridine, a known nucleoside antimetabolite used in the treatment of colorectal cancer, explains Ramón Eritja, Scientific Director of NANBIOSIS U29 from CIBER-BBN and IQAC-CSIC.

The authors used the NANBIOSIS Unit 29 Oligonucleotide Synthesis Platform (OSP) to prepare short oligonucleotides that form a tetrameric structure that is recognized by cancer cells facilitating the specific delivery to the tumor cells. Once inside of the cells, the oligonucleotides generate the active drug by nuclease degradation as a Trojan horse.

Article of reference:

Clua A, Fàbrega C, García-Chica J, Grijalvo S, Eritja R. Parallel G-quadruplex Structures Increase Cellular Uptake and Cytotoxicity of 5-Fluoro-2′-deoxyuridine Oligomers in 5-Fluorouracil Resistant Cells. Molecules. 2021; 26(6):1741. [DOI] 

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Three Nanbiosis units work in the development of new sensors for the better detection of the fungus P. jirovecii, responsible for Pneumocystis pneumonia

Researchers from the CIBER-BBN have succeeded in developing detection systems for Pneumocystis jirovecii, an atypical fungus responsible for very serious pneumonia in immunosuppressed patients. These results, published in the journal Nanomaterials, are the result of collaboration between the CIBER-BBN groups led by Laura Lechuga, Ramon Eritja and Ramón Martínez Máñez, and the CIBERESP group led by Enrique J. Calderón.

The researchers acknowledge the paricipation of three NANBIOSIS units of CIBER-BBN:

The detection of the fungus in patients, who may be asymptomatic carriers until they develop pneumonia, is currently carried out using the PCR technique, requiring several hours, adequate facilities and qualified personnel to detect it. Now, the application of Nanotechnology has allowed the development of more sensitive and efficient biosensors to detect specific sequences corresponding to pathogens responsible for infectious diseases in a shorter time and without the need for large infrastructures.

In this case, a specific sequence corresponding to the gene belonging to the ribosomal subunit (mtLSU rRNA) of the P. jirovecii fungus has been detected using hairpin-shaped capture probes. These specific probes, as pointed out by Dr. Aviñó, a researcher at CIBER-BBN at the IQAC-CSIC, “are more efficient and are capable of recognizing a specific genomic sequence of the fungus and forming very stable triplex structures that can be detected on different platforms. biosensor “.

Laura Lechuga’s team at ICN2, through the use of an optical biosensor based on SPR technology, has detected in real time and without the use of markers, P. jirovecii in bronchoalveolar lavages and nasopharyngeal aspirates with a detection limit of nM level and in just a few minutes.

Likewise, the group led by Ramón Martínez-Máñez, scientific director of CIBER-BBN and principal investigator of the IQMA-IDM group at the Universitat Politècnica de València, has used the strategy of molecular gates composed of an anodic albumin matrix to develop a sensor capable of to efficiently detect real P. jirovecii samples without previous amplification steps in as little as one hour.

“These advances in the diagnosis of PCP have great potential for the development of highly sensitive point-of-care devices using direct patient samples and applicable in a wide variety of settings,” says the CIBERESP group leader. Enrique J. Calderón from the Virgen del Rocío University Hospital in Seville.

The researchers also emphasize that these techniques are very selective and can discriminate patients with other respiratory diseases derived from other microorganisms, thus allowing a more reliable diagnosis of infectious diseases.

Articles of reference:

Calvo-Lozano, O., Aviñó, A., Friaza, V., Medina-Escuela, A., S Huertas, C., Calderón, E. J., Eritja, E., Lechuga, L. M. (2020). Fast and accurate pneumocystis pneumonia diagnosis in human samples using a label-free plasmonic biosensor. Nanomaterials, 10(6), 1246. https://doi.org/10.3390/nano10061246

Pla, L., Santiago-Felipe, S., Aviñó, A., Eritja, R., Ruiz-Gaitán, A., Pemán, J., Friaza, V., Calderón, E.J. Martínez-Máñez, R., Aznar E. (2020). Triplex hybridization-based nanosystem for the rapid screening of Pneumocystis pneumonia in clinical samples. Journal of Fungi, 6(4), 292. https://doi.org/10.3390/jof6040292

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