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News U26

News U26

NANBIOSIS research to fight cancer

Twenty years ago, the 4 February was declared World Cancer Day with the global challenge of cancer would not be forgotten. Since then, huge progress has been made to understand, prevent, diagnose, and treat cancer.

NANBIOSIS as an ICTS (Singular Scientific and Technical infrastructures) for biomedical research plays a very important role in the fight against cancer. Some examples of the work carried out during the last year, are bellow:

Unit 20 of NANBIOSIS  at VHIR, works in several proyects reletaed to cancer as  H2020-NoCanTher: magnetic nanoparticles against pancreatic cancer through the use of hyperthermia combined with conventional treatment. H2020-Target-4-Cancer: nanotherapy based on polymeric micelles directed against specific receptors of tumor stem cells in colorectal cancer. H2020-DiamStar: nanodiamonds directed against leukemia for the potentiation of chemotherapy. FET-OPEN EvoNano: in silico and tumor-tumor models for the prediction of PK / PD and tumor efficacy of antitumor nanomedicines against tumor stem cells.

The activities of U1 of Protein Production Platform (PPP) are also strongly committed with several projects devoted to develop new, more selective and more efficient antitumoral drugs, with antimetastatic effects.
oordinated action between units U1 of Protein Production Platform (PPP),
U18 of Nanotoxicology and U29 of Nucleic Acid Synthesis, shows promising results in development of nanopharmaceuticals with a high degree of efficacy for the treatment of metastases in colon cancer

Unit 6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit  is also working on a joined initiative between CIBER-BBN and CIBER-ONC to improve the current ex vivo immune cell expansion systems to help introduce immunotherapies such as the adoptive cell therapies, which have shown complete remissions of terminal cancer patients, to the clinics overcoming the limitation of having enough therapeutic cells with novel Nanobiomaterials. Researchers of Unit 6 and researchers of Laboratory of Translational Research in Child and Adolescent Cancer from the Vall d’Hebron Research Institute (VHIR), are working on a project financed by the Spanish Government and CIBER-BBN, for the development of a new nanomedicine for the treatment of high-risk neuroblastoma, one of the most frequent childhood cancers.

In our unit U26. NMR: Biomedical Applications II,  several studies for cancer biomarker discovery are being carried out. NMR studies on biofluids for the design of novel strategies for diagnosis support, easily transferable into the clinical practice, are being developed in biofluids in the context of cancer. Urine is one of the most easily obtainable biofluid and is a non-invasive source of biomarkers. Among these studies, we can mention the good discrimination achieved between urine from bladder cancer patients before surgery (cancer) and urine after surgery (free of cancer) and in the follow up of the disease, to monitor relapses

Some of the results of these researchs have been published in scientific magazines of high impact as for exemple;

Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer Alba Loras, Cristian Suárez-Cabrera, M. Carmen Martínez-Bisbal, Guillermo Quintás , Jesús M. Paramio, Ramón Martínez-Máñez,
Salvador Gil and José Luis Ruiz-Cerdá. Cancers 2019, 11, 686; doi:10.3390/cancers11050686

Nanostructured toxins for the selective destruction of drug-resistant human CXCR4+ colorectal cancer stem cells Naroa Serna, Patricia Álamo, Prashanthi Rameshef, Daria Vinokurovaef, LauraSánchez-García, Ugutz Unzueta, Alberto Gallardo, María  Virtudes Céspedes, Esther Vázquez, Antonio Villaverde, Ramón Mangues, Jan Paul Medema. . Journal of Controlled Release.  Volume 320, 96-104, 2020 https://doi.org/10.1016/j.jconrel.2020.01.019

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering Voltà-Durán, E., Cano-Garrido, O., Serna, N. et al. CSci. China Mater.63, 147–156 (2020). https://doi.org/10.1007/s40843-019-9582-9

Engineering Secretory Amyloids for Remote and Highly Selective Destruction of Metastatic Foci, María Virtudes Céspedes  Olivia Cano‐Garrido  Patricia Álamo  Rita Sala  Alberto Gallardo  Naroa Serna  Aïda Falgàs  Eric Voltà‐Durán  Isolda Casanova  Alejandro Sánchez‐Chardi  Hèctor López‐Laguna  Laura Sánchez‐García  Julieta M. Sánchez  Ugutz Unzueta  Esther Vázquez  Ramón Mangues  Antonio Villaverde . Advanced Materiasls Número de artículo: 1907348 , Dec. 2019 https://doi.org/10.1002/adma.201907348

Artificial Inclusion Bodies for Clinical Development Julieta M. Sánchez  Hèctor López‐Laguna  Patricia Álamo  Naroa Serna  Alejandro Sánchez‐Chardi  Verónica Nolan  Olivia Cano‐Garrido  Isolda Casanova  Ugutz Unzueta  Esther Vazquez  Ramon Mangues  Antonio Villaverde, Advanced Science. 2019 https://doi.org/10.1002/advs.201902420

Nanostructured Nucleolin-Binding Peptide for Intracellular Drug Delivery in Triple-Negative Breast Cancer Stem Cells Mireia Pesarrodona, Laura Sánchez-García, Joaquin Seras-Franzoso, Alejandro Sánchez-Chardi, Ricardo Baltá-Foix, Patricia Cámara-Sánchez, Petra Gener,  José Juan Jara, Daniel Pulido, Naroa Serna, Simó Schwartz Jr. Miriam Royo, Antonio Villaverde, Ibane Abasolo, Esther Vazquez ACS Applied Materials & Interfaces DOI: 10.1021/acsami.9b15803  

Nanostructure Empowers Active Tumor Targeting in Ligand‐Based Molecular Delivery López‐Laguna, H., Sala, R., Sánchez, J. M., Álamo, P., Unzueta, U., Sánchez‐Chardi, A., Serna, N., Sánchez‐García, L., Voltà‐Durán, E., Mangues, R., Villaverde, A., Vázquez, E., . Part. Part. Syst. Charact. 2019, 36, 1900304. https://doi.org/10.1002/ppsc.201900304

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A new fluorescent probe for NO

Nitric oxide is a component of the pollutant nitrogen oxides (NOx) responsible of different environmental negative effects. However, due to its physiological effects, NO has been used in different therapeutic applications. Thus, the inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that finds its best applications in pediatrics, by transiently improving oxygenation in respiratory failure and persistent pulmonary hypertension. The initial recommended concentration of iNO in these treatments is 20 ppm. Higher concentrations do not increase its effectiveness and are associated with a higher incidence of methemoglobinemia and formation of nitrogen dioxide. In consequence the control of iNO concentration is of great interest.

Silvia Rodríguez-Nuévalos, Margarita Parra. Samuel Ceballos, Salvador Gil and Ana M.Costero, researchers of CIBER-BBN, Politecnic University of Valencia and University of Valencia were interested in detecting nitric oxide by different protocols and decided to study the Aggregation Induced Emission (AIE) phenomena as a possible transduction mechanism for detecting nitric oxide, compatible with aqueous media.

To sum up, a new probe capable of selectively detecting nitric oxide was prepared and evaluated. The probe is a tetraphenylethylene derivative and the transduction mechanism is really based on the Aggregation Induced Emission (AIE) phenomena. The click reaction catalyzed by NO modifies the steric volume of the TPE substituents inducing clear changes in the fluorescence emission. A limit of detection of 15 ppm has been determined and the linearity range appears between 20 and 80 ppm suggesting that the probe could be useful to control the use of iNO. Other gases such as NO2, CO2, CO and SO2 do not induce appreciable changes in the measure range. The probe works properly in MeOH:H2O media.

NMR spectra were registered at the Unit 26 of ICTS “NANBIOSIS”: NMR: Biomedical Applications II of ICBER-BBN at the Universitat of Valencia led by Ramón Martínez Máñez and Salvador Gil Grau.

Article of reference:

Silvia Rodríguez-Nuévalos, Margarita Parra. Samuel Ceballos, Salvador Gil, Ana M.Costero. A nitric oxide induced “click” reaction to trigger the aggregation induced emission (AIE) phenomena of a tetraphenyl ethylene derivative: A new fluorescent probe for NO. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY.  Vol: 388. 2020  https://doi.org/10.1016/j.jphotochem.2019.112132

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Nanomedicine: how to get drugs to the place where they have to act.

At the beginning of June, the Jury of the Rei Jaume I 2018 Awards, formed by Nobel Prize winners, businessmen and scientists, met in Valencia to choose the winners.

Today has taken place the ceremony of delivery of the 30th edition of the awards presided over by King Felipe VI. Among the six winners, in the category of New Technologies was Ramón Martínez Mañez, Scientific Director of the CIBER-BBN and Unit 26 of NANBIOSIS.

Coinciding with its thirtieth anniversary, the Rei Jaume Foundation has produced a series of videos of interviews with the winners. In this video, Ramón Martínez Mañez, Scientific Director of Unit 26 of NANBIOSIS, who has received the Rei Jaume I Award for New Technologies, talks about the two major areas in which he works and other topics such as the recognition of science and the need to recover the talent of researchers who go out of Spain and a better connection between research and the company. Some of his answers are the following:

One of our lines of research is in the field of sensors: systems based on nanotechnology for the detection of substances such as the presence of pathogens that may be harmful to health. The other major area is nanomedicines for the controlled release of drugs, one of the fundamental ideas of nanomedicine is how to get drugs to the place where they have to act.

Recognition in science is obtained if your works are cited, having social recognition is much more difficult.

We are a good country in science but we are a country in the second division in the transfer of science to the companies, it is needed more investment so that the products end up coming to the market or so that more research is done in collaboration with companies in Spain.

It is good to leave Spain, not necessarily to succeed but to see how they work in other places. The problem that exists today is that it is very difficult to return to Spain and this is a pity because there are very well educated and very good people who stay abroad.

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The revolution of nanomedicine by Ramón Martínez Mañez

Ramón Martínez Mañez, Scientific Director of Unit 26 of NANBIOSIS NMR: Biomedical Applications II, will be next Monday, November 5 at 7 pm at the Headquarters of Alicante City (San Fernando, 40), where he will impart the conference “The scientific revolution of Nanomedicine,”

The professor of Inorganic Chemistry of the UA and director of the Nanotechnology laboratory, Javier García Martínez, will present the meeting, organized by the Fundación Premios Rey Jaume I and the UA, with the collaboration of the Valencian Agency and Innovation and the Classroom of Science and the Technology of the University of Alicante.

Ramón Martínez-Máñez, director of the Institute for Research in Molecular Recognition and Technological Development (IDM) and scientific director of the Center for Biomedical Research in Networks in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) has been recently awarded King Jaume I of New Technology 2018. The jury of the King Jaume I awarded for New Technologies valued the “exceptional contributions” by Ramón Martínez-Máñez in the development of nanosensors with application in food technology and medicine, as well as “the high scientific quality and social impact of his work “and, for these reasons, he was awarded this award in June 2018. He is also a scholar of the American Chemical Society and the Royal Spanish Society of Chemistry. He was awarded in 2016 by the latter with the prize for Excellence Research

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Ramón Martínez Máñez Master class on Nanomedicine at the Act of the Academic Opening year 2018-2019  of Spanish university

On September 25, the Polytechnic University of Valencia hosted the Solemn Act of the new Academic Opening year 2018-2019  of Spanish universities, coinciding with the commemoration of its 50th anniversary. This institutional act was chaired by S.M. King Felipe VI, the Minister of Science, Innovation and Universities, Pedro Duque, and the President of the Generalitat Valenciana, Ximo Puig, among many other authorities.

Ramón Martínez Máñez, has been in charge of teaching the master class of the new academic year. Ramón Martínez is professor of the Department of Chemistry of the UPV and director of the Interuniversity Research Institute of Molecular Recognition and Technological Development, besides Scientific Director of CIBER-BBN and Scientific Director of NANBIOSIS U26 NMR: Biomedical Applications II

In the master class, Martínez Máñez explained that nanomedicine aims to “identify diseases in their early stages at the cellular and molecular level through the use of nanodevices and contrast systems” in order to “provide an early diagnosis and, therefore, improve the prognosis of the disease“. Ramón Martínez Mañez, Rei Jaume I Award for New Technologies 2018 has underlined that, nanomedicine “is already a well-established area of ​​knowledge that seeks to apply the continuous advances of nanotechnology to medicine” and that “there are numerous studies that demonstrate its great capacity for the development of new diagnostic devices, new systems for the controlled release of drugs and materials suitable for the development of tissues.  In fact, as indicated “there are already in the market biomedical solutions based on nanotechnology such as nanoformulated drugs.” For the professor of the UPV, “we do not know what is the future of medicine, but without a doubt nanotechnology will play an important role in its development and, although we do not know who will carry out these advances, undoubtedly, the research developed in the university it will play a fundamental role “.

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Nano-carrier to release drugs into damaged cells

Senescent cells are damaged cells that do not perform their normal roles anymore but that are not dead –hence they are commonly known as zombi cells. These cells interfere with the functioning of the tissue in which they accumulate. Senescence is a cell program that is triggered by many types of damage and senescent cells are present in many diseases. They accumulate in diverse types of tissues during aging, thus contributing to the progressive deterioration associated to aging. Eliminating these zombi cells is one of the challenges facing science today.

In the Cellular Plasticity and Disease lab headed by the ICREA researcher Manuel Serrano at the Institute for Research in Biomedicine (IRB Barcelona) and supported by “la Caixa” Banking Foundation, the researchers devise strategies to eliminate senescent cells. In a study published in EMBO Molecular Medicine, they present a proof of principle of a drug delivery system with selectivity for tissues that harbour senescent cells.

In collaboration with a team headed by Ramón Martínez-Máñez, Scientific Diirector of NANBIOSIS Unit 26 NMR: Biomedical Applications II ,  the IRB Barcelona scientists have exploited a particular hallmark of senescent cells in order to design a delivery system that specifically targets them. They have demonstrated its efficacy in cells in vitro and in two experimental mouse models, namely pulmonary fibrosis and cancer. These diseases are characterized by the presence of damaged cells, and in the case of cancer this is particularly true after treatment with chemotherapy.

In these models, the senescent cells take up the carrier more efficiently than other cells and once inside the cell the casing of the carrier degrades to release the drug cargo. When the nano-vehicles contained cytotoxic compounds, the senescent cells were killed and this resulted in therapeutic improvements in mice with pulmonary fibrosis or with cancer.

“This nano-carrier may pave the way for new therapeutic approaches for serious conditions, such as pulmonary fibrosis or to eliminate chemotherapy-induced senescent cells,” explains Manuel Serrano. Another outcome of this study is that these nano-carriers could be used for diagnostic tests of senescence as they can transport a fluorescent compound or marker.

This study, performed by IRB Barcelona in collaboration with the Universidad Politécnica de Valencia, CNIO, the University of Cambridge, CIBER-BBN, and the company Pfizer in the US, is a step towards achieving the capacity to eliminate senescent cells. Developing tools to specifically eliminate senescent cells is currently a central goal for many pharmaceutical companies, among them the one set up by Manuel Serrano himself together with Ramón Martínez-Máñez and José Ramón Murguia, Senolytic Therapeutics, which is located at the Barcelona Science Park and in Boston.

The study has been funded by “la Caixa” Banking Foundation, the Botín Foundation, the European Research Council, CRUK Cambridge Centre Early Detection Programme, the Ministry of Economy and Competitiveness/ERDFs and the Catalan Governmen

Daniel Muñoz‐Espín, Miguel Rovira, Irene Galiana, Cristina Giménez, Beatriz Lozano‐Torres, Marta Paez‐Ribes, Susana Llanos, Selim Chaib, Maribel Muñoz‐Martín, Alvaro C Ucero, Guillermo Garaulet, Francisca Mulero, Stephen G Dann, Todd VanArsdale, David J Shields, Andrea Bernardos, José Ramón Murguía, Ramón Martínez‐Máñez, Manuel Serrano A versatile drug delivery system targeting senescent cells EMBO Molecular Medicine (2018) DOI 10.15252/emmm.201809355

Image: The figure shows two views, frontal and lateral, of the image obtained by CT of the lungs of a mouse with fibrosis (grey areas) before and after receiving nano-therapy directed at senescent cells. (Guillem Garaulet and Francisca Mulero, CNIO)

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NANOMEDICINE APPLICATIONS IN DRUG DELIVERY AND TARGETING: NANBIOSIS – NANOMED Industrial Forum

Yesterday took place in Barcelona, at Barcelona School of Management, Universitat Pompeu Fabra, a meeting of resarch groups and units of NANBIOSIS and CIBER-BBN and companies in the third B2B Forum organized by NANBIOSIS, in this case together with NANOMED SPAIN.

Thirteen companies and twelve groups from CIBER-BBN and CCMIJU (ten of them coordinating NANBIOSIS units) got together to explain, through short presentations of ten minutes, those lines of their work aimed at finding synergies and potential collaborations in the area of Nanomedicine apllications in drug delivery and targeting. There was also a talk by a  representative of CDTI (Spanish National Center for Industrial and Technological Development) to explain the financing opportunities for the companies as well as a presentation by the NANBIOSIS Coordinator, Jesús Izco, to show the new Cutting Edge Biomedical Solutions offered by the ICTS-NANBIOSIS

After lunch, the groups and companies had the opportunity to discuss in more detail, during bilateral interviews coordinated by NANBIOSIS a, those aspects that had attracted their attention, as well as, in some cases, to draw potential collaborations. The event was successfully developed with 45 attendees and more than 50 individual B2B mettings.

 

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Infections such as Candiasis will be detected in 30 minutes

Ramón Martínez Máñez, Elena Aznar and Ángela Ribes, researchers of Unit 26 of NANBIOSIS, NMR: Biomedical Applications II, in collaboration with researchers from the Universitat Politècnica de València, with the Universitari i Politècnic La Fe Hospital and the Rovira i Virgili University, have developed a new material that allows to detect quickly and with a high sensitivity infections caused by Candida albicans, a type of fungus that can be found in different biological fluids, causing opportunistic infections such as Candidemia or Invasive Candidiasis.

According to Javier Pemán, head of section and head of the Mycology Unit of the Microbiology Service of the Hospital Universitari i Politècnic La Fe,” infections are difficult to identify early, very frequent in most Intensive Care Units (ICUs) and represent an important challenge in critical patients”.

Currently, these infections are diagnosed by culturing the biological fluid to be studied and subsequent identification of yeast isolated by different microbiological techniques whose results can take between 3 and 4 days. Meanwhile, with this new material and method – patented by the UPV, the CIBER, the Hospital La Fe and the URV – the diagnostic time is reduced to only 30 minutes.

“The tests can be carried out quickly and practically in the same consultation in which the patient sample is taken, significantly reducing the equipment necessary to detect the presence of Candida albicans. Our work facilitates the diagnosis and medical decision-making, through the use of a powerful and fast tool to detect the infection”, says Ramón Martínez Máñez, scientific director of the CIBER-BBN and director of the IDM Institute at the UPV, as well as scientific director of NANBIOSIS U26.

Nanoporous films with molecular doors

The material developed by the CIBER-BBN research gourp, led by Ramón Martínez Máñez, is about nanoporous alumina films that incorporate “molecular doors” based on oligonucleotides. The characterization has been carried out in Unit 26 of NANBIOSIS, NMR: Biomedical Applications II.

“They are constituted by a porous inorganic support that is loaded with a dye and by simple strands of DNA. These strands are anchored to the surface of the support and act as “molecular doors” that inhibit the release of the indicator “, explains Ramón Martínez Máñez.

In addition, according to Professor Lluis Marsal, from the Rovira i Virgili University, the type of support used greatly simplifies the methodology of the experiment.

On how to detect the infection, Professor Martínez Máñez explains that the simple strands of DNA are selected taking into account a specific sequence of Candida albicans.

“When the presence of the DNA of this fungus is noticed, it interacts with the molecular door, the pores open and that is when the release of the dye that is inside the nanoporous support takes place, thus detecting the infection,” adds Elena Aznar , researcher of the CIBER-BBN in the IDM-UPV.

The diagnostic material is now in the clinical validation phase, thanks to the funding obtained through the CANDI-GATE project granted by the Polytechnic University of Valencia and the La Fe Health Research Institute and led by M. Angeles Tormo and Elena Aznar and through the CANDI-EYE valuation project granted by the CIBER-BBN and led by Elena Aznar.

Patent of reference:

“Porous material for the detection of Candida albicans, diagnostic method that uses it and method of preparation of it”. Spanish application pattent P201731069 2017-09-05.

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Rey Jaime I Award of New Technologies to Ramón Martínez Mañez

Ramon Martínez Mañez, Scientific Director of NANBIOSIS U 26 Biomedical Applications II and Scientific Director of CIBER-BBN, has received the Rey Jaime I Award of New Technologies 2018.

Rey Jaime I Awards are granted (in xis cathegories) to people who stand out in their field of work and who have developed most of their professional activity in Spain. Candidates must be nominated by third parties and must prove their qualities. They are recognized as the most prestigious awards for the activity carried out in Spain. It is one of the best paid prizes in the country. Each of them is endowed with 100 thousand euros and a gold medal. The winners of each category are committed to allocate a part of the prize amount to research and entrepreneurship in Spain.

The jury  of the Jaime I Award for New Technologies (integrated by 18 Nobel prizes) has valued Martínez Mañez “exceptional contributions” in the development of nanosensors with applications in food technology and medicine. Among them, he has indicated the colorimetric labels for the assessment of the freshness of food, the devices for the simple detection of the Human Papilloma Virus (HPV) and the nanostructures of controlled release of active principles against the fruit fly.

In addition, the jury remarked that the “high scientific quality” of his work has been applied in different technological fields with social impact.

Ramón Martínez-Máñez is a university professor, director of the Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM).  He has published a total of 393 articles in different scientific journals and has a very prominent presence in the most significant journals in the field of mustidisciplinary chemistry, such as the Journal of the American Chemical Society or Angewandte Chemie International Edition Nature Communicationsand, having been cited more than 17,000 times (web of Science, 19,874 times in Google Scholar), with an average of more than 42 citations per article, and has an h index of 60 (web of Science, h index of 63 in Google Scholar). Moreover, he has coordinated 99 national and European projects and has achieved “very reliable” sensors for clinical diagnosis, detect changes in the environment and control food quality, with applications in agriculture and nanomedicine.

Currently, his research group is working on the development of nanometric devices with “molecular doors” for the controlled release of drugs. The mesoporous nanoparticles studied are able to retain a charge within their pore system and deliver it when applied a chemical, physical or biochemical stimulus. These particles have been used, for example, for the selective release of cytotoxins for the elimination of cancer cells and bacteria, and also for the release of certain drugs in senescent cells. In addition, the group of Martínez Máñez works in the development of molecular probes for the detection, through changes in color and fluorescence, of elements of environmental and biomedical interest such as drugs, nerve gases, certain types of cells, etc.

Also María Vallet Regí, head of the CIBER-BBN group at the Complutense University of Madrid, has been awarded the Rey Jaime I of Basic Research. Thus, two of the six Awards granted by this institution this year recognize the work of researchers of the CIBER-BBN, partner of NANBIOSIS.

Video by UPVTV
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I Forum on Emerging Technologies organized by CIBER

On May 8th, will take place in Madrid, at the Assembly Hall Ernest Lluch of the Instituto de Salud Carlos III, organized by CIBER Internationalization Platform (CIBER-BBN, CIBERER, CIBERES) the I Forum on Emerging Technologies.

The objective of this meeting is to promote the exchange of ideas and scientific knowledge among the CIBER research groups with the aim of generating new collaborations for participation in cross-cutting projects and the development of border technologies. The content of the forum, centered on the type of technology and possibilities it offers, is structured in a program of lectures and scientific debates whose final objective is the discussion and the joint generation of ideas. This first edition of the forum will be focused on Gene Therapy, Nanotechnologies and Omic Technologies-Big Data.

Some Units of NANBIOSIS will participate:

  • José Luis Pedraz, Scientific Director of  Unit 10 Drug Formulation, will speak of “Development of non-viral vectors for gene therapy
  • Laura Lechuga, Scientific Director of Unit 4  Biodepositon and Biodetection, will talk about “Nanodispositive biosensors for advanced clinical diagnosis
  • Rosa Villa, Scientific Director of Unit 8 Micro–Nano Technology, Ramón Martínez, Scientific Director of Unit 26 NMR Biomedical Applications II and Esther Pueyo, researcher of U27 High Performance Computer will moderate the sessions.

 

Programme and registration details

 

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