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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 Record” journal 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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Experimental & molecular medicine: a new article with NANBIOSIS U17

ICTS-NANBIOSIS. UNIT 17 CONFOCAL MICROSCOPY SERVICE. (CIBER-BNN. UNIVERSITY OF ALCALÁ)

The UAH research groupTranslational research of chronic diseases associated with aging and kidney disease has recently published an article in which unit NANBIOSIS unit 17 and Leica SP5 confocal microscope has had a great contribution

Located in the Support Center for Research in Medicine and Biology, Faculty of Medicine and Healthe Sciences, University of Alcalá (UAH). The Unit is equipped with a Leica TCS-SP5 confocal microscope. The confocal module is equipped with three spectral detection channels, AOBS (Acousto-optical beam splitter) and a resonant scanner system that allows analysis at high speed and resolution and makes possible the analysis of dynamic in vivo physiological processes in short periods, significantly improving the survival of living biological samples by shortening the exposure times to lasers. Includes an argon laser, a He/Ne laser, a DPSS laser diode and a violet excitation laser. The microscope is coupled to a cell incubation kit that allows multi-position time-lapse experiments. The equipment includes a workstation and four software for acquisition and analysis, which allow 3D visualizations, co-location studies, FRAP (Fluorescent Recovery after Photo-bleaching), FLIP (Fluorescent Loss in Photobleaching) and FRET (Fluorescence Resonant Energy Transfer). The equipment allows 3D characterization in detail of living cells and tissues through the use of different fluorochromes, expression and localization of molecules in 2/3D, colocalization and interaction of proteins or other types of molecules; endocytosis and intracellular transport, in situ hybridization with fluorescent probes, interaction studies between cells and materials, etc.

The unit provides researchers with a wide array of routine and specialized services as well as the latest advances in microscopy, including technical and scientific support to scientists for the study of cell/tissue biology, physiology and pathogenesis of diseases.

Article of reference

Campillo, S., Bohorquez, L., Gutiérrez-Calabrés, E., García-Ayuso, D., Miguel, V., Griera, M., Calle, Y., de Frutos, S., Rodríguez-Puyol, M., Rodríguez-Puyol, D., & Calleros, L. Indoxyl sulfate- and P-cresol-induced monocyte adhesion and migration is mediated by integrin-linked kinase-dependent podosome formation Experimental & molecular medicine, 2022, 54(3): 226–238. https://doi.org/10.1038/s12276-022-00738-8

Abstract

Cardiovascular disease is an important cause of death in patients with chronic kidney disease (CKD). Protein-bound uremic toxins, such as p-cresyl and indoxyl sulfate (IS), are poorly removed during hemodialysis, leading to vascular endothelial dysfunction and leukocyte extravasation. These processes can be related to dynamic adhesion structures called podosomes. Several studies have  indicated the role of integrin-linked kinase (ILK) in the accumulation of integrin-associated proteins in podosomes. Here, we investigated the involvement of ILK and podosome formation in the adhesion and extravasation of monocytes under p-cresol (pc) and IS exposure. Incubation of THP-1 human monocyte cells with these toxins upregulated ILK kinase activity. Together, both toxins increased cell adhesion, podosome formation, extracellular matrix degradation, and migration of THP-1 cells, whereas ILK depletion with specific small interfering RNAs suppressed these processes. Interestingly, F-actin colocalized with cortactin in podosome cores, while ILK was colocalized in podosome rings under toxin stimulation. Podosome Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) and AKT protein depletion demonstrated that monocyte adhesion depends on podosome formation and that the ILK/AKT signaling pathway is involved in these processes. Ex vivo experiments showed that both toxins induced adhesion and podosome formation in leukocytes from wild-type mice, whereas these effects were not observed in leukocytes of conditional ILK-knockdown animals. In summary, under pc and IS stimulation, monocytes increase podosome formation and transmigratory capacity through an ILK/AKT signaling pathway-dependent mechanism, which could lead to vascular injury. Therefore, ILK could be a potential therapeutic target for the treatment of vascular damage associated with CKD.

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ISO 9001:2015 Quality Certification for the Soft Scientific and Technical Service at ICMAB and Unit

The aim of the quality certification obtained is to ensure the quality of the service provided and to continue with its improvement and extension to future services.

The Scientific and Technical Service for the characterization of nano and biomaterials, the Soft Lab, run by the Nanomol Research Unit of the Institute of Materials Science of Barcelona (ICMAB, CSIC), and which is part of Unit 6 of the ICTS Nanbiosis, and CIBER-BBN, aims to offer characterization services of micro- and nanostructured soft molecular materials to the entire scientific community that requires them.

To this end, the Soft technical service has several laboratories at ICMAB equipped for the study of the stability of solutions, the study of particle size distribution, the determination of the density of porous solids, or the study of biomolecular interactions of materials, among others.

Following a series of audits that evaluated the Soft service’s characterization services, the service was awarded the ISO 9001:2015 quality certification at the end of 2021.

The ISO standard is the most widespread and recognised reference system for the implementation and certification of a quality management system, based on three axes: continuous improvement, customer satisfaction and involvement of all stakeholders.

The principles of quality management taken into account in the evaluation are: focus on the customers; management leadership; commitment with the people; process approach; continuous improvement; evidence-based decision making; relationship management.

Therefore, the Soft service is responsible, as reflected in the quality commitment agreement, for providing its services with the highest quality standards, and for the continuous monitoring of various indicators to assess the degree of compliance with the quality commitments, including the customer satisfaction degree. These statistics will be part of the corresponding quality reports and reviewed by the management team, as set out in the Soft/U6 Nanbiosis quality policy.

Congratulations to the Soft service and to all the Nanomol team for achieving this quality certification! 

ndp quatsomes mirna 03

Soft Service ICMAB / U6 Nanbiosis

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Researchers of NANBIOSIS U8 highlighted in the World Health Day

In the Picture: Gemma Gabriel and Rosa Villa

World Health Day is celebrated every year on 7 April (on the aniversary of the World Health Organization constitution) to raise awareness about the ongoing health issues that concern people across the world.

This year, Xarctec Salud has called the attention on patients with brain diseases and spinal cord injuries and has highlighted the GAB Lab. Biomedical Applications Group of the IMB-CNM-CSIC and CIBER-BBN, the group, led by Rosa Villa, coordinates unit 8 ICTS NANBIOSIS of Micro-nano Technology Unit.

https://youtu.be/wiA5oFc6Q48

The Xartec Salut is a network, led by CREB UPC, made up of 47 research groups that belong to 17 different institutions. It aims to be a catalyst for R+D+I in the field of HealthTech by Fostering the exchange of knowledge between research groups, institutions, hospitals and companies, promoting company creation and new career opportunities and offering more efficient instruments for technology transfer.

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Targeting of the breast cancer stem cells to improve the treatment of triple negative breast cancer

On April 1st PhD candidate Patricia Cámara Sánchez defended her doctoral thesis entitled “Targeting of the breast cancer stem cells to improve the treatment of triple negative breast cancer“, where ICTS-Nanbiosis Unit 20 participated in the in vivo assays. The thesis was supervised by Dr. Ibane Abasolo  (scientific director of Unit 20 from CIBER-BBN and VHIR). Nanbiosis was also present within the jury, with Dr. Ana Paula Candiota (scientific coordinator of Unit 25 from CIBER-BBN and UAB) acting as secretary.

Patricia Cámara graduated as biochemist, did the master’s degree in Translational Biomedical Research from VHIR-UAB. Shortly after, started the PhD, which was aimed at improving the treatment of very deadly subtype of breast cancer by using different nanoformulations to specifically target the cancer stem cells. The now doctor Cámara-Sánchez screened up to 20 small drugs with anti-cancer stem cell activity, found synergistic ratios with conventional chemotherapeutic agents, and finally developed polymeric micelles encapsulating selected drugs. During the discussion of the dissertation, the need of additional in vivo assays was highlighted, as well as the potential use of MR provided by the U25, to explore non-invasively the metabolomic differences between cancer stem cells and regular cancer cells.

‘I’m very grateful for the opportunity to have been part of this amazing project. It has been a very enriching experience’, she explains. ‘After 5 years of research, I finish the PhD feeling very proud of having contributed to the fight against this aggressive subtype of breast cancer’, she adds. From now on, new research lines will bring forward the synergies between both units of NANBIOSIS, reinforcing a collaboration started several years ago and reflected in joint papers.

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1st Meeting with Cystic Fibrosis Patiens (NanoBioCel -ARNASA)

Cystic Fibrosis is a genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. It is a genetic, degenerative and chronic disease, with a population incidence is 1 in 5,000, so it is considered among the so called “Rare Diseases”

The most common symptoms are continuous colds, repeated infections, decreased lung capacity, impossibility of fat absorption and malnutrition

As there is no cure for the disease, daily treatment is the only option to have an acceptable quality of life

The NanoBioCell Research Group, which coordinates unit 10 of NANBIOSIS of the CIBER-BBN and the UPV/EHU, has a wide experience in comprehensive research into effective therapies for the treatment of cystic fibrosis and related diseases has organized the ‘First meeting with cystic fibrosis patients’ in the collaboration with ARNASA Bizkaia, (the Cystic Fibrosis Association of Bizkaia, made up of affected people, their families and volunteers who collaborate with the association)

Registration is free here. After registration you will receive a link to the online meeting

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Colloidal phenomena in COVID-19

Transmission electron microscope image of SARS-CoV-2 (National Institute of Allergy and Infectious Diseases https://www.niaid.nih.gov)

The special volume (No. 55) of the journal Current Opinion in Colloid and Interface Science reviews the implications of colloidal science in the phenomenology of COVID-19, for which the techniques available in NANBIOSIS U12, “Nanostructured liquid characterization unit” , are relevant.

Two articles to highlight in this special volume:

  • Airborne transmission of the virus through droplets, and the effect of evaporation and sedimentation. Airborne transmission is determined by the settling time, that is, the time it takes for droplets to be in the air before settling. Evaporation increases the settling time by reducing the mass of the droplets. In fact, the small droplets can, depending on their solute content, evaporate almost completely and remain in the air for a long time. Considering that viruses possibly remain infectious for hours in the form of aerosols, the formation of droplet nuclei can substantially increase the infectious viral airborne load. The article reviews the physical-chemical factors that control the evaporation and sedimentation times of droplets and play an important role in determining the risk of airborne infection. (https://www.sciencedirect.com/science/article/pii/S1359029421000558)

  • The interactions between surfactants and viruses, which act on different components such as the lipid envelope, the membrane proteins (envelope) and the nucleocapsid proteins. Surfactants play very important roles, either directly, as in disinfection, or as carrier components of drug delivery systems for prophylaxis or treatment. By designing tailor-made surfactants and consequently advanced formulations, an increasingly effective use of surfactants can be expected, either directly as antiviral compounds or as part of more complex formulations. (https://www.sciencedirect.com/science/article/pii/S1359029421000637)

In summary, colloid science can contribute in a multidisciplinary strategy to fight pandemics.

By Carlos Rodriguez Abreu, Scientific Director of NANBIOSIS U12

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Is it possible to communicate microorganisms from different kingdoms? Yes, it is, using “Nanotranslators”

CIBER, March 28 2022

Researchers from the Polytechnic University of Valencia (UPV) and the CIBER-BBN has demonstrated, for the first time, the potential of using “translator” nanoparticles to facilitate communication between different types of cells or microorganisms. His study could have application in multiple fields, especially in the medical field for the prevention and treatment of cancer.

“We have shown that it is possible to communicate microorganisms from different kingdoms using nanoparticles as translators. The nanoparticles process a message produced by the first type of cells (bacteria) and transform it into an understandable message for the second type of cells (yeast) that respond to it. In this way, the information flows from the emitting cells (bacteria) to the nanodevice and from the latter to the receiving cells (yeast), which allows communication between two microorganisms that would not otherwise interact. This is an advance in the design of nanoscale communication systems and opens the door for the development of future applications”, says Ramón Martínez Máñez, researcher at the Institute for Molecular Recognition and Technological Development (IDM) at the UPV and scientific director of the CIBER-BBN and Scientific Director of NANBIOSIS U26,”Biomedical Applications II”.

Among these future applications, the UPV-CIBER-BBN team highlights the possible regulation of the interactions between bacteria and human cells, for example, to prevent infections, kill bacteria or modulate our intestinal microbiome, and for the treatment of diseases such as cancer. “In this case, it would help cells of our immune system to recognize cancer cells more efficiently, regulating the interactions between them,” says Antoni Llopis, a CIBER-BBN researcher at the IDM Institute.

It could also be useful for designing particles that make it possible for plants and fungi to communicate with each other, which could help develop new plant protection strategies. “We could establish communication between plant cells and other microorganisms in their environment in order to prevent pests or use them as a treatment to improve plant performance,” says Ángela Morellá, a researcher at the Institute for Molecular Recognition and Technological Development (IDM) and study co-author.

In any case, the UPV and CIBER-BBN team insist that the results obtained are incipient –“it is a proof of concept”, they emphasize-, although they open a path with great potential for the field of micro/ nanotechnology and synthetic biology.

“Perhaps the biggest challenge will be reading whether the communication between those two kingdoms has been successful or not. In our study, we have used the expression of fluorescent protein by receptor cells, which facilitated the monitoring of the process. The development of future applications will require more advanced methodologies to allow the monitoring of chemical communication processes in complex biological environments”, concludes Ramón Martínez Máñez.

Article of reference

Beatriz de Luis, Ángela Morellá-Aucejo, Antoni Llopis-Lorente, Javier Martínez-Latorre, Félix Sancenón, Carmelo López, José Ramón Murguía, and Ramón Martínez-Máñez. Nanoprogrammed Cross-Kingdom Communication Between Living Microorganisms. Nano Letters 2022 22 (5), 1836-1844. DOI: 10.1021/acs.nanolett.1c02435

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New equipment installed in NANBIOSIS U20

NANBIOSIS, U20. In Vivo Experimental Platform, led by Dr. Ibane Ibasolo, has been updated and improved as a result of its participation in the project FICTS1420-20, selected by the MICINN for co-financing by the FEDER Program in ICTS 2014-2020 (Equipment for setting standardized immunotoxicology assays for the U20 -NANBIOSIS I17 Action of the Investment Plan-)

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The results of POSITION II highlighted by CORDIS: A pan-European alliance for the next generation of smart catheters

In the picture: microencapsulated cardiospheres 10X Captured Brightfield with DM_RGB_Brightfield with DM

The European project POSITION-II has been selected for publication in the ‘Results in Brief’ section of the Community Research and Development Information Service (CORDIS) website. CORDIS is the European Commission’s primary source of results from the projects funded by the EU’s framework programmes for research and innovation (FP1 to Horizon 2020).

The resulting short article has now been published on the CORDIS website in six languages.

The European project POSITION II “A pilot line for the next generation of smart catheters and implants” is an alliance of European leaders, united to improve technology and offer cheaper, easier to use, more efficient and technologically advanced catheters by incorporating sensors and real-time positioning and monitoring systems. This new generation of catheters will improve the treatment of multiple pathologies, through new therapeutic tools such as cell therapy and tissue engineering implemented in the project by the U10 Drug Formulation of the ICTS Nanbiosis, which is integrated in the NanoBioCel group of CIBER-BBN and UPV/EHU.

The following actions have been carried out in NANBIOSIS U10 Drug Formulation during the execution of the project:

– Isolate, expand and characterize cardiosphere-derived cells (CDCs). CDCs were  isolated from porcine cardiac tissue, and their  release profile of immunomodulatory factors was determined.

– To optimize the encapsulation conditions of CDCs in alginate microcapsules.

– Evaluate whether the physical and chemical properties of the encapsulated CDCs were suitable for the catheter developed in the project.

– Determine that the secretion profile of trophic factors did not change in CDCs after encapsulation.

– Provide the TME Lab group and NANBIOSIS U13 of CIBER-BBN and the University of Zaragoza with the microcapsules and encapsulated CDCs required for their mechanical characterization and to evaluate the behavior of the capsules in the catheter and in the animals at the NANBIOSIS units of Center for Minimally Invasive Surgery in Extremadura (CCMIJU). Other collaborations during the execution of the project were established with the Fraunhofer EMFT group in Germany and with the Spanish company IberHospitex, manufacturer of the catheters.

Other related news:

Results of the POSITION-II Project “A pilot line for the next generation of smart catheters and implants”

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