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Nucleic Acids Chemistry, new book release by Ramon Eritja

Ramón Eritja, Scientific Director of NANBIOSIS Unit 29 Oligonucleotide Synthesis Platform (OSP) has just published a new book “Nucleic Acids Chemistry, modifications and conjugates for Biomedicine and Nanotechnology“, Anna Avinó, Scientific Coordinator of NANBIOSIS Unit 29 is also a writer of the book.

The book “Nucleic Acids Chemistry” takes the most important aspects of the methodology of oligonucleotides synthesis, that is currently expanding by the endorsement of a dozen of new medicines, such as the first medicine based on interfering RNA for the control of LDL and cholesterol in blood that will facilitate the decrease of cardiovascular illnesses.

The writing of the book has been directed by Dr. Ramon Eritja, of Centro de Investigación en Red de Nanomedicina (CIBER-BBN) and is Research Professor at Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), being its director between 2012-2017. The co-authors are Carme Fàbrega, Anna Aviñó, Santiago Grijalvo, Andreia F. Jorge, from IQAC-CSIC, Carlos González from Instituto de Química Física Rocasolano (IQFR-CSIC) and Raimundo Gargallo from University de Barcelona  The book began to be written in mid-2019, although most of the book was written during the lockdown.

In the last five years, an expansion of technologies based on DNA and RNA in diagnosis and therapeutic use has been produced, and it has been very important in the research of quick solutions to avoid the COVID pandemic and, predictably, the research group’s environment has led the development of several solutions, like biosensors for the direct detection of SARS-CoV-2.

A former PhD student of Ramon Eritja group, Dr. Ramón Güimil García, Head of Synthetic Oligonucleotides bei BioNTech, has participated in the development of the BioNTech-Pfizer mRNA vaccine. Another doctor, Brendan Manning, formed member of the group, has participated in the development of a diagnosis kit named Sherlock, which uses the CRISPR-Caspasa system for the detection of the virus that causes COVID.

Dr Erija completed his doctoral thesis at the University of Barcelona directed by Dr. Ernest Giralt on the subject of peptide synthesis. In 1984 he carried out his first postdoc with Dr. Itakura at the Beckman Research Institute of City of Hope in Los Angeles where the production of the first synthetic genes was carried out, highlighting the production of synthetic insulin that, with the name of humulin, solved the problems generated from the use of swine insulin. In 1986 she completed the second postdoc with Dr. Caruthers at the University of Colorado at Boulder. In this laboratory, phosphoramidites were developed, which are the reagents used today for the production of synthetic DNA and RNA. Upon his return to Barcelona, ​​he joined the CSIC Research and Development Center where he organized the first research group in our country focused on oligonucleotide synthesis. In 1984 he moved to the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany) to direct for 5 years one of the most prestigious groups in DNA and RNA Chemistry in Europe. Upon his return to Barcelona, ​​he was part of the Barcelona Institute for Biomedical Research (IRB Barcelona) and was recognized as a group of excellence by the CIBER-BBN. In 2012 he moved to the IQAC-CSIC to occupy the direction of the institute until 2017.

Refernce:

Nucleic Acids Chemistry – Modifications and Conjugates for Biomedicine and Nanotechnology Edited by: Ramon Eritja. De Gruyter | 2021 DOI: https://doi.org/10.1515/9783110639537

The book can be purchased here: link

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New patented peptide to allows the faster internalization of drugs within cells and the design of more effective therapeutic nanoconjugates

Researchers of NANBIOSIS Unit 20 In vivo Experimental Platform of CIBER-BBN and Vall d’Hebron Research Institute (VHIR) have patented a peptide that, in comparison to the current standard treatment, is much faster, internalizes much more, and does not cause any toxicity.

The membrane of a cell is an effective barrier that hinders the targeted delivery of molecules, such as therapeutic compounds. During the last years, several strategies have been developed to get the molecules into the cell interior but, in general, the methods developed still show a low efficacy and / or toxicity. “The use of therapeutic nanoconjugates such as nanomedicines facilitates the transport and delivery of drugs in target cells, but often with less efficiency than we would like,” says Dr Simó Schwart Jr, head of the Scientific Director of NANBIOSIS Unit 20 and the CIBBIM-Nanomedicine group: Direction i Alliberament Farmacològic del Vall d’Hebron Research Institute (VHIR)/CIBER-BBN.

Given the need to get more drugs or proteins into cells, one of the alternatives to be able to increase the amount that enters their interior more quickly is what is known as Cell penetrating peptides or cellular internalizing peptides, small sequences of amino acids that have the ability to interact with the plasma membranes of cells and, as a result of this interaction, make it easier to internalize the cargo they carry. An example of application would be when an internalizing peptide binds to a therapeutic nanoconjugate, achieving a greater capacity for the nanoconjugate to enter the cell interior and, therefore, to release the drugs it carries into the cells.

Until now, one of the most important internalizing peptides used has been known as TAT. Now, a team of researchers led by Dr. Schwartz Jr, has discovered a sequence common to a family of peptides that significantly outperforms the TAT results and facilitates the cellular internalization of nanoconjugates in a very significant way. These peptides are derived from a membrane protein called CD300 which has a very high capacity to interact with sphingomyelin, a lipid found in all plasma membranes and also in intracellular organelles. “The peptides in our patent”, explains Dr. Simó Schwartz Jr, “are derived from an extracellular part of CD300, which has a high capacity to bind sphingomyelin. Compared to the current standard treatment, TAT, CD300f7 is much faster, internalizes much more, and does not cause any toxicity. The use of these peptides in nanomedicine therefore facilitates and increases the internalization process of all the cargo they carry. This means that we are able to introduce drugs into cells in less time and in greater quantities ”. The results of this discovery not only allow for faster internalization within the cell, but also open the door to designing much more effective therapeutic nanoconjugates.

Souce of information: VHIR news

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Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity

Researchers of Nanbiosis U8 Micro– Nano Technology Unit, from CIBER-BBN and IMB-CNM-CSCIC have published an article in Nature Communications on Graphene arrays for long-term and wireless mapping of epicortical brain activity. A collaborative work in the framework of the Brain Com and Graphene EU projects. The article mentions the participation of NANBIOSIS-ICTS.

Graphene active sensors have demonstrated promising capabilities for the detection of electrophysiological signals in the brain. Their functional properties, together with their flexibility as well as their expected stability and biocompatibility have raised them as a promising building block for large-scale sensing neural interfaces. However, in order to provide reliable tools for neuroscience and biomedical engineering applications, the maturity of this technology must be thoroughly studied. Here, we evaluate the performance of 64-channel graphene sensor arrays in terms of homogeneity, sensitivity and stability using a wireless, quasi-commercial headstage and demonstrate the biocompatibility of epicortical graphene chronic implants. Furthermore, to illustrate the potential of the technology to detect cortical signals from infra-slow to high-gamma frequency bands, we perform proof-of-concept long-term wireless recording in a freely behaving rodent. Our work demonstrates the maturity of the graphene-based technology, which represents a promising candidate for chronic, wide frequency band neural sensing interfaces.

Article:

Garcia-Cortadella, R., Schwesig, G., Jeschke, C. et al. Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity. Nat Commun 12, 211 (2021). https://www.nature.com/articles/s41467-020-20546-w

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A rare genetic bone pathology is identified from massive sequencing methods

The Andalusian Center for Nanomedicine and Biotechnology (BIONAND) and the Center for Biomedical Research Network in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), both partners of NANBIOSIS, in collaboration with the International Registry of Skeletal Dysplasias of the University of California (Los Angeles) and Masaryk University, of the Czech Republic have described a new genetic disease of the skeleton using a precision medicine strategy.

This disease consists of extreme bone fragility with lack of mineralization and skeletal deformation associated with joint dislocation and heart disease, as well as a lung deficiency that causes perinatal lethality -at the time of birth-. Using massive sequencing methods – of all genes – researchers have identified the mutations that caused a type of rare bone pathology, specifically, those of the ‘LAMA5’ gene, responsible for encoding a cellular matrix protein that surrounds blood vessels in skeletal tissues.

“Our scientific team has spent years investigating rare genetic syndromes that affect the skeleton in order to provide a medical solution to patients with difficult diagnosis and treatment,” explains the researcher from the Department of Cell Biology, Iván Durán, lead author of this study, whose results have been published in the scientific journal ‘EBIOMEDICiNE’.

According to the expert, precision medicine is the key to discovering what genetic and molecular factors cause this type of pathology and, therefore, understanding the mechanism that causes them and being able to develop personalized therapies.

Thus, researchers have also described the disease mechanism by generating cellular models by gene editing, mimicking the mutations in ‘LAMA5’, with the aim of confirming whether these are the origin and knowing the molecular process that triggers the problem. These cellular models have been generated by genetic editing with CRISPR, introducing mutations that cause a null or hypomorphic gene.

“Thanks to these models, we discovered a new signaling pathway that governs the formation of the skeleton – so that the bone grows and remains healthy – which means that our work has not only led to the discovery of a new disease, but to a mechanism unprecedented that can be exploited for common bone disorders ” –explains Durán, “the presence of ‘LAMA5’ between cells that direct skeletal formation indicates, therefore, that the appearance of signals from special blood vessels can be a very effective weapon for bone repair and regeneration. Blood vessels not only provide irrigation to the bone, but also carry signals and house niches of stem cells that can be mobilized to induce a regenerative process. ‘LAMA5’ seems to be a key component for harboring pericyte-type stem cells”.

Article of reference:

Barad M, Csukasi F, Kunova-Bosakova M, Martin J, Zhang W, Taylor SP, Dix P, Lachman R, Zieba J, Bamshad M, Nickerson D, Chong JX, Cohn DH, Krejci P, Krakow D, Duran I. Mutations in LAMA5 disrupts a skeletal noncanonical focal adhesion pathway and produces a distinct bent bone dysplasia. 2020 EBioMedicine. Nov 23;62:103075. doi: 10.1016/j.ebiom.2020.103075

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Inkjet Priting Technology, Manufacture and validation of electrochemical sensors in medical applications

Miguel Zea, a member of the NANBIOSIS U8 Micro– Nano Technology Unit presents a video explaining his research is based on the manufacture and validation of electrochemical sensors in medical applications: –“Using InkJet printing I have made sensors in different plastics and paper. Also using a novel approach in each sensor. I have made two pH sensors using novel Platinum and polymer inks and also a cortisol sensor on paper”.

With this video, Miguel Zea, participates in the second edition of ‘I investigate, I am CSIC’. It is a competition hold by The Spanish National Research Council (CSIC) for its doctoral students to disseminate their doctoral thesis. Through short videos of maximum duration of 3 minutes, predoctoral scientists explain their research and results for the public in general

Here you can see the video and vote with a like!

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Outstanding Young Researcher Award at ICESS 2021 to Konstantinos Mountris (NANBIOSIS U27).

Konstantinos Mountris researcher from the BSICoS group of CIBER-BBN and I3A at the University of Zaragoza has been granted the Outstanding Young Researcher Award at the International Conference on Computational & Experimental Engineering and Sciences (ICCES) in relation with the work Radial Point Interpolation Mixed Collocation (RPIMC) Method for The Solution of Reaction-Diffusion Equation in Cardiac Eletrophysiology (for the simulation of myocardial infarction).

This work was already recognized in the Congress of Computing in Cardiology (CinC) held recently where Konstantinos Mountris and Esther Pueyo have received the Maastricht Simulation Award (MSA). Konstantinos Mountris acknowledged the contribution of NANBIOSIS U27 High Performance Computing :“using the HPC services of NANBIOSIS U27 we were able to validate the RPIMC method as a promising alternative to Finite Element Method performing large-scale simulations of myocardial infarction in biventricular swine models“

Related news: Understanding human heart behaviour with mathematics and engineering.

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New Scanning Electron Microscope and on line Seminar to explain it for internal and external accesses on NANBIOSIS U12

A new Scanning Electron Microscope (Hitachi TM-4000 Plus II) has been installed at the Nanostructured liquid characterization unit of NANBIOSIS ICTS (Unit 12) of CIBER-BBN and IQAC-CSIC.

An online seminar will be given by Susana Vilchez on January 14th at 12h to explain the various features, functions and capabilities of this new instrument, Tabletop Scanning Electron Microscope Hitachi TM-4000 Plus II, that is open for both internal and external users.

Those interested in attending the seminar can contact unit 12 of NANBIOSIS:

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NANBIOSIS Unit 2 obtains the Biosafety Level 2 Accreditation

The laboratory of NANBIOSIS Unit 2 from IQAC-CSIC and CIBER-BBN has obtained the biosafety level 2 accreditation, which allows the laboratory to work with biological agents classified in the risk group 2.

Biological containment level 2 (NBS2) laboratories are generally required to work with any derivative of human blood or other primates, body fluids (especially when they are visibly contaminated with blood), cell lines, or tissues in which has uncertainty about the presence of an infectious agent.

Also, the group participates in the COVID project “Point-of-care tests for the rapid detection of SARS-CoV-2 (POC4CoV)”, funded by the CSIC. This project involves the handling of swabs and serum samples from both positive and negative SARS-CoV-2 patients. Lluïsa Vilaplana, member of research group Nb4D of CIBER-BBN and IQAC-CSIC, led by Dra. M. Pilar Marco, wich Coordinates NANBIOSIS U2, has coordinated the process to obtain the accreditation.

The laboratory has an antechamber or clean locker room, a card-controlled entry system and a space for the storage of materials and reagents. It has also an independent air conditioning system, a specific air renewal system and a biosafety cabin type 2A, with HEPA filter. In addition, it is equipped with a suitable lighting system, an emergency lighting system and a large observation peephole on the door.

In addition to this specific equipment, the laboratory is equipped with an inverted microscope, centrifuge, thermostatic bath, stirrers, incubators, refrigerator and autoclave for sterilization and waste management.

The Nanobiotechnology for Diagnosis (Nb4D) research group , focus the research on the development of biomarkers for the diagnosis of infectious diseases. Nowadays, the group participates in five research projects related to this topic. These projects involve working with clinical samples for the detection of the pathogens Pseudomonas aeruginosa (Gram – type bacteria) and Staphylococcus aureus (Gram + type bacteria), both classified in risk group 2.

Source of information: IQAC-CSIC Communication

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