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News U29


Dr. Ramon Eritja, Scientific Director of NANBIOSIS unit 29 of Oligonucleotide Synthesis Platform (OSP) and Dr. Santiago Grijalvo researcher at NANBIOSIS unit 12 of Nanostructured liquid characterization, from CIBER-BBN and IQAC-CSIC, together with Dr. Andreia F. Jorge, from Coimbra Chemistry Centre (CQC), acting as guest editors of journal Pharmaceutics, of MDPI Publisher, welcome authors to submit their articles on special issues on Recent Trends in Oligonucleotide Based Therapies.

In the past few decades, significant efforts have been made towards the clinical application of oligonucleotides. However, the potential of the therapeutic applications of RNA-based strategies have recently been spotlighted after the first approval of mRNA vaccines in response to COVID-19 pandemic. These molecules have the power to tackle targets that are usually considered to be “undruggable” by blocking the translation or transcription of a specific gene by stimulating the degradation of a particular messenger RNA.

This Special Issue aims to collect reviews, original research articles, and short communications covering innovative strategies in the design, synthesis, and characterization of therapeutic oligonucleotides as well as advances in their delivery based on nanotechnologies. Research concerning the study of sequence-specific protein–DNA/RNA interactions will be also considered.

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form.

For all the informations and instructions about the Special Issue, please visit this MDPI page

Deadline for submissions: 31 December 2022

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Wide representation of NANBIOSIS research in NALS 2022 and best Oral Presentation to Eloi Parladé

During the last 27-29 April, the 3rd International Conference on Nanomaterials Applied to Life Sciences 2022 (NALS 2022) has taken place in the Excellence Campus of Universidad de Cantabria in Santander (Spain), organized by the University of Cantabria and Institute Valdecilla-IDIVAL.

NALS 2022 has been a multidisciplinary conference series sharing new results and ideas in the fields of biosensors, lab on a chip, drug delivery nanopharmacy. nanobiotechnology, intelligent nanomaterials, magnetic materials, nanotoxicity, antimicrobials, novel applications of 3d bioprinting and nanoimaging.

NANBIOSIS has been represented at this edition by members of several of its units, among them we must highlight the set of four oral communication presented by members of the Nanobiotechnology group-Unit 1 of NANBIOSIS “Protein Production Platform (PPP)”, from CIBER-BBN and IIB-UAB the talks were delivered by:

Eloi Parladé: “Development of ion-dependent microscale secretory granules for nanomedical applications

Carlos Martínez-Torró: “Design of a human GFP-like protein scaffold for targeted nanomedicines

Eric Voltá Durán: “Antitumoral nanoparticles with multiple activities, a close reality

Jan Atienza-Garriga: “Characterization of protein-only NPs containing amps and analysis of their protection with liposomes and micelles

They summarized a wide area of the team activities on the design of protein-based protein materials for clinical uses, produced by means of diverse types of cell factories. In particular, antimicrobial peptides, cytotoxic proteins with antitumoral targeting and drug-carrying scaffold proteins are engineered to confer self-assembling properties as either microparticles or nanoparticles, that can be further functionalized with chemical drugs through covalent binding. Microparticles are of special interest as they can be used as slow drug delivery systems for nanostructured drugs upon subcutaneous administration. Alternatively, nanoparticles can be also presented as embedded in liposomes or other micellar structures that stabilize them for enhanced performance.

Three NANBIOSIS units, namely U1 (Protein Production Platform), U18 (Nanotoxicology) and U29 (Oligonucleotide Synthesis Platform), have supported the presented research, which has been executed in a highly cooperative way.

Among all the excellent contributions by the team, it is worthy to stress that the prize for the best Oral Presentation was granted to Dr Eloi Parladé.

Other talk by researchers from NANBIOSIS were “Antioxidant-loaded polymeric NPs prepared by nano-emulsion templating for the management of neurological diseases” by Santiago Grijalvo, from NANBIOSIS U12 and  “Exploiting GSH oxidation with nanocatalysts to promote cancer cell death” by Javier Bonet-Aletá from NANBIOSIS U9

On the other hand, Jesús Santamaría,  Scientific Director of NANBIOSIS U9 was a Keynote Speaker in the Conference with the talk: “A change of paradigm in cancer therapy? Using catalysts to make drugs inside the tumor, rather than trying systemic chemotherapy”

NALS 2022 has been an excellent conference, with presentations covering a wide range of topics in nanomaterials for health, and a great opportunity for our researchers, especially for young’s, to let know their collaborative work, as well as make new connections on common research interests, thanks to the good socializing opportunities afforded by the scheduling of the organization conference.

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Dr. Anna Aviñó, Scientific Coordianator of NANBIOSIS unit 29 of Oligonucleotide Synthesis Platform (OSP) and Dr. Carme Fàbrega from the Nucleic Acid Chemistry group from CIBER-BBN and IQAC_CSIC, together with Dr. Claudia Riccardi from the University of Naples Federico II, Dr. Stefania Mazzini from University of Milan, and Dr. Raimundo Gargallo from the University of Barcelona, acting as guest editors of the journal Frontiers in Chemistry, welcome authors to submit their articles on special issues on Nucleic Acid-Based Aptamers in Therapeutics and Diagnostics.

Nucleic acid‐based aptamers are short DNA or RNA sequences able to adopt specific three‐dimensional architectures. The high affinity and selectivity shown for a selected target, as well as the wide range of molecular targets, make aptamers a valuable alternative to antibodies in several biological applications.

Oligonucleotide-based aptamers have become an attractive tool not only in molecular biology research but also in modern medicine as precision instruments for molecular diagnostics, as sensing device and in therapy (as drugs or drug-delivery systems). Numerous improved methodologies for their selections and various applications, such as bioimaging, diagnoses, molecular therapies, and nanotechnology, have been reported to date.

This Research Topic will concentrate on the latest development’s nucleic acid-based aptamer chemistry. We encourage authors to submit original research and review articles dealing with all the aspects of aptamer research, including aptamer selection technology, engineering/modification strategies, characterization, development, and/or application of aptamers in therapeutics and diagnostics.

Manuscripts should be submitted on line on the following link.

Deadline for submission: 26 May 2022

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The coming revolution: synthetic DNA and RNA for therapeutic and diagnostic applications

The discovery of the mRNA vaccines for the treatment of coronavirus, as well as new medicines for the treatment of genetic diseases, has been important in the quest of solutions for undrugable diseases in an unexpected short-time.

Thus, the chemical modifications of nucleic acids with diagnostic and therapeutic purposes is now a reality, a revolution that promises to give hopes on unsolved medical problems or optimize previous approaches, largely due to the research push for the development of mRNA vaccines against SARS-CoV-2 infection.

Now, the prestigious The Chemical Recordjournal has invited the Nucleic Acids Chemistry group, of IQAC-CSIC and CIBER-BBN and belonging to the Global Health Platform of CSIC, to describe the advances and modificacions of the nucleic acids in the last decade. The article, authored by Dr. Carme Fàbrega, Dr. Anna Aviñó and Dr. Ramon Eritja (coordinator and director, respectively, of Unit 29 of ICTS NANBIOSIS), reports the development of synthetic DNA and RNA for therapeutic and diagnostic applications.

The article describes the most important results from the Nucleic Acid Chemistry group in this area covering the international context that surrounded these studies. These include the development of modifications in potentially therapeutic oligonucleotides to enhance nuclease resistance as well as improving cellular uptake and avoiding side effects, and the advances in the use of DNA nanostructures in the controlled deposition of matter in surfaces and their potential application as drug delivery systems is reported.

Moreover, the article has been selected to illustrate the front cover of The Chemical Record, a journal of the Chemical Society in Japan, with a suggestive image that shows the research activity in this area. The back image is the three dimensional reconstruction of a DNA array described by the group of Dr. Seeman obtained by A. Garibotti in Barcelona. On the top the crystal structure of the Argonaute protein from the Protein Data Bank is shown. This protein is a natural player that helps the therapeutic action of RNA molecules. 

Read the full article in this link.

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DNA nanotechnologists are in mourning

At the end of the XXth century Nanotechnology appeared as one of the more powerful technologies for the future. At that time material sciences were able to produce nanomaterials with exquisite size control and atomic force, microscopy was able to visualize objects in the nanoscale and photolithography arrived to their physical limits in the preparation of computer chips threatening Moore’s law. This empirical law saying that as transistor components shrank, the number per chip doubled about every 18 months, was acting from 1971  (Intel’s first chip) to billions in the present times. 

At these times, one crucial development was the discovery of the first self-assembling DNA structures, leaded by Ned Seeman, who died recently at age 75. Being a crystallographer interested in DNA-protein structures, Ned though that a good way to obtain crystals of DNA-protein complexes was to prepare crystal networks of DNA where proteins bind. (In the classical approach of obtaining protein crystals small oligonucleotides bind). In this way in 1982 he described the idea of making lattices from DNA junctions. In 1991 he obtained a DNA cube, the first tridimensional DNA nanostructure receiving the 1995 Feynman Prize in Nanotechnology. But the most impressive development was the so-called “DNA tile systems” published in 1998.

The figure shows a bidimensional array made by his former Ph.D. student Alejandra Garibotti in our laboratory in Barcelona. In the tile system two or more tiles (each one made out of 5 oligonucleotides) are designed to self-assemble one next to the other by their sticky ends making a large lattice or bidimensional crystal having a tunable shape and size defined by the tiles.

Later on in 2009, Ned was able to demonstrate the achievement of three-dimensional DNA crystals. These developments settle the foundations for the development of DNA origami, DNA computation, DNA nanoelectronics and DNA nanorobotics earning the Kavli Prize in Nanoscience in 2010. The immense creativity of Ned is not only an active value for mankind but also an example for old and new scientists.

By Ramón Eritja, Scientific Director of NANBIOSIS U29, January 10th, 2022

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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 project by NANBIOSIS researchers, focused on COVID-19 detection and therapy, selected in ‘La Marató’ research program

The Scientific Commission of ‘La Marató TV3’ has seleced the project entitled “Diagnosis and treatment of Sars-Cov-2 by triplex formation”, led by Ramon Eritja, Scientific Director of NANBIOSIS Unit 29 Oligonucleotide Synthesis Platform (OSP) from CIBER-BBN and IQAC_CSIC to be financed with € 398,750.00. Verónica Noé from the Fundació Bosch i Gimpera Universitat de Barcelona, ​​the CIBERESP researcher Enrique Calderón Sandubete, from the Virgen del Rocío University Hospital and María Valeria Grazú Bonavía, from the Institute of Nanoscience and Materials of Aragón, INMA (CSIC- UNIZE) also participate in this project.

The edition of this solidarity initiative promoted by the Corporació Catalana de Mitjans Audiovisuals, raised more than twelve million euros to finance research against COVID-19. The project was selected, among the 229 submitted, to receive funding for its development.
Our project wants to solve two important problems in the fight against the COVID-19 pandemic: the first is how to quickly and specifically detect people infected by this virus; and the second is that right now we do not have a effective therapy specifically designed to be used against the virus that causes COVID-19 “explains Dr. Eritja.

The project will try to solve both problems using synthetic oligonucleotides with high and specific affinity for viral RNA. “In recent years, a dozen oligonucleotides have been approved by Health agencies (EMA and FDA) for the treatment of genetic diseases such as Duchene muscular dystrophy as well as metabolic diseases such as familial hypercholesterolemia. In the project we will use specific oligonucleotides, procuced at NANBIOSIS U29, to bind viral RNA that could be used in vitro for the selective capture and diagnosis of the SARS-.COV-2 virus, but also in vivo to inhibit the replication of viral RNA “adds Ramón Eritja.

The call for grants from ‘La Marató’ was carried out, exceptionally, between the months of December and January. Until May, the 229 candidate projects have been reviewed electronically, following a process of proven rigor and transparency, coordinated by the Catalan Agency for Quality and Health Evaluation, in which 95 international evaluators have participated. The assessment, among other aspects, of the quality, the methodology, the scientific, health and social relevance, the innovative value and the viability of the candidate works has determined which projects have been financed with the resources of La Marató 2020.

With this new edition from La Marató, the solidarity project of the Catalan Audiovisual Media Corporation and the Foundation since 1992 an amount of € 216 million have been awarded and a total of 949 research projects hve been promoted, with participation of 9,350 researchers have participated.

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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 CellsMolecules. 2021; 26(6):1741. [DOI] 

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NANBIOSIS Scientific Women in the International Day of Women and Girls in Science

Today February 11 is the International Day of Women and Girls in Science, a day to raise awareness of the gender gap in science and technology.

According to the United Nations, while yet women and girls continue to be excluded from participating fully in science, science and gender equality are vital to achieve the internationally agreed development goals, including the 2030 Agenda for Sustainable Development. Thus, in recent years, the international community has made a great effort to inspire and promote the participation of women and girls in science.

NANBIOSIS wants to acknowledge  the efforts made by scientific women who struggle every day to contribute their bit to Science and highlight their essential role in nowadays research. Especially we want to recognize the work of scientists women involved in NANBIOSIS, whatever is the nature of their contribution: technical, scientific development, management, coordination, direction, etc; just to mention some examples:
Neus Ferrer and Mercedes Márquez in the Scientific Direction and Coordination of Unit 1 Protein Production Platform (PPP)
Pilar Marco and Nuria Pascual in the Management and Scientific Coordination of U2 Custom Antibody Service (CAbS) 
Miriam Royo in the Scientific Direction of U3 Synthesis of Peptides Unit
Nora Ventosa and Nathaly Segovia in the Scientific Direction and Technical Coordination of U6 Biomaterial Processing and Nanostructuring Unit
Isabel Oliveira and Teresa Galán in the Coordination of U7 Nanotecnology Unit
Rosa Villa and Gemma Gabriel in the Management and Scientific Coordination of U8 Micro – Nano Technology Unit
Gema Martínez in the Scientific Coordination of U9 Synthesis of Nanoparticles Unit
Fany Peña in the Scientific Coordination of U13 Tissue & Scaffold Characterization Unit
Mª Luisa González Martín and Margarita Hierro in the of Direction and Scientific Coordination of U16 Tissue & Scaffold Characterization Unit
Gemma Pascual and Isabel Trabado in the Coordination of the U17 Confocal Microscopy Service
Isolda Casanova in the Scientific Coordination of U18 Nanotoxicology Unit
Beatriz Moreno in the Scientific Direction of Unit 19 Clinical tests lab
Ibane Abásolo in the Scientific Coordination of Unit 20 In Vivo Experimental Platformt
Verónica Crisóstomo in the Scientific Direction of Unit 24 Medical Imaging 
Ana Paula Candiota in the Scientific Coordination of Unit 25 Biomedical Applications I 
Maria Luisa García in the Scientific Direction of U28 NanoImaging Unit from Bionand, recently incorporated to NANBIOSIS, Anna Aviñó in the Scientific Coordination of U29 Oligonucleotide Synthesis Platform (OSP) – and

Nerea Argarate in the coordination of NANBIOSIS

Thanks to all of you and your teams!

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Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles

In the frame of the collaboration of three units of NANBIOSIS, researchers of CIBER-BBN Groups proposed a strategy to simultaneously deliver anticancer drug pairs, composed by a tumor-targeted protein nanoparticle and an antiproliferative drug, with specific activ-ity for the same type of cancer.

These three units are:

The results on the investigation have been published in an article entitled “Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles”· by Acta Biomaterialia

The researchers have explored the possibility to conjugate tumor-targeted cytotoxic nanoparticles and conventional antitumoral drugs in single pharmacological entities using CXCR4-targeted self-assembling protein nanoparticles based on two potent microbial toxins, the exotoxin A from Pseudomonas aeruginosa and the diphtheria toxin from Corynebacterium diphtheriae, to which oligo-floxuridine and monomethyl auristatin E respec- tively have been chemically coupled.

The resulting multifunctional hybrid nanoconjugates, with a hydro- dynamic size of around 50 nm, are stable and internalize target cells with a biological impact. Although the chemical conjugation minimizes the cytotoxic activity of the protein partner in the complexes, the concept of drug combination proposed is fully feasible and highly promising when considering multiple drug treatments aimed to higher effectiveness or when facing the therapy of cancers with acquired resistance to classical drugs.

Thus, these results open a wide spectrum of opportunities in nanomedical oncology.

Article of reference:

Eric Voltà-Durán, Naroa Serna, Laura Sánchez-García, Anna Aviñó, Julieta M. Sánchez, Hèctor López-Laguna, Olivia Cano Garrido, Isolda Casanova, Ramón Mangues, Ramon Eritja, Esther Vázquez, Antonio Villaverde, Ugutz Unzueta Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles. Acta Biomaterialia, Volume 119, 1 January 2021, Pages 312-322), 57746-57756 https://doi.org/10.1016/j.actbio.2020.11.018 

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