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Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP.2013.1.2-2 | Award Amount: 13.07M | Year: 2014

Increase in antibiotic resistance is a global concern worldwide. The project NAREBs main objective is the optimization of several nanoformulations of antibacterial therapeutics in order to improve the therapy of multi-drug resistant (MDR) tuberculosis (TB) and MRSA infections in European MDR patients. NAREB will address the problem of drug bioavailability inside the infected macrophages, transport across the bacterial cell wall, and avoidance of escape mechanisms (expressed by the pathogen). The success of the utilization of nanoparticles in the improvement of drug targeting in other diseases opens the way for novel applications in nanotechnology-based treatments aimed at controlling MDR-TB and MRSA. Specific objectives to achieve the main goal are: (i) Screening of different combinations of antibiotic drugs (small chemical molecules and/or biomacromolecules - glycopeptides) with nanocarriers (lipid, polymeric, biopolymeric); (ii) Loading of Transcription Factor Decoys (TFDs) designed to block the expression of essential bacterial genes in compatible nanoparticle systems and their testing as novel antibacterials; (iii) In vitro and in vivo testing of the best therapeutic combinations in relevant experimental models and using innovative bioimaging; (iv) Improved formulations of multifunctional particles containing selected antibiotics and TFDs for increasing the bioavailability of active molecules in the site of infection (targeting strategy, adapted route of administration) (v) Assessing safety, regulatory and production (GLP/GMP) aspects in relation with the most promising nanoformulations; (vi) Clinical Development Plan for the preparatory work for the subsequent clinical testing of the selected nanoformulations. The project NAREB brings together 15 partners (including 4 SMEs and 1 industry) from 8 EU Member and Associated States with outstanding complementary expertise, ranging from material engineering to molecular biology, pharmacology and medicine.

Fratila R.M.,University of Zaragoza | Mitchell S.G.,University of Zaragoza | Del Pino P.,CIC Biomagune | Grazu V.,University of Zaragoza | And 3 more authors.
Langmuir | Year: 2014

The field of nanotechnology applied to medicine (nanomedicine) is developing at a fast pace and is expected to provide solutions for early diagnosis, targeted therapy, and personalized medicine. However, designing nanomaterials for biomedical applications is not a trivial task. Avoidance of the immune system, stability in physiological media, control over the interaction of a nanomaterial with biological entities such as proteins and cell membranes, low toxicity, and optimal bioperformance are critical for the success of the designed nanomaterial. In this Feature Article we provide a concise overview of some of the most recent advances concerning the derivatization of gold and iron oxide nanoparticles for bioapplications. The most important aspects relating to the functionalization of gold and iron oxide nanoparticles with carbohydrates, peptides, nucleic acids, and antibodies are covered, highlighting the recent contributions from our research group. We suggest tips for the appropriate (bio)functionalization of these inorganic nanoparticles in order to preserve the biological activity of the attached biomolecules and ensure their subsequent stability in physiological media. © 2014 American Chemical Society.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: BG-03-2014 | Award Amount: 4.75M | Year: 2015

Surfactants and emulsifiers constitute an important class of chemical agents that are widely used in almost every sector of modern industry. The huge market demand is currently met almost exclusively by synthetic, mainly petroleum-based, chemical products, which are usually non-biodegradable and mostly toxic or GM plant based products (used in foods), which are undesirable by some end-users. Their biologically produced counterparts (i.e. bio-surfactants and bio-emulsifiers) offer more green sustainable alternatives. This has led to a number of manufactures, looking for ways to increase competitiveness through searching for underexploited sources such as the marine environment. Our objectives are to develop (1) innovative approaches in discovering, characterizing and producing novel marine-derived bio-surfactants from a large bacterial collection (greater than 500 strains) housed at Heriot Watt University, originally isolated from various coastal and open ocean waters around the world, (2) novel, economic, and eco-friendly end-products with commercial applications in order to replace synthetic counterparts, and (3) to demonstrate the functionality of new product development for commercial exploitation. Our collection consists of novel bacterial species, originally isolated for their ability to degrade oils, with proven promise in this respect. For this reason, our consortium (consisting of academic institutions, industrial companies and end-users) offering a wide range of expertise, will address the technical bottlenecks for meeting our objectives, namely those of marine resource identification, sustainable supply, discovery pipeline and efficient production in biological systems. The relevance of our proposal to the work programme is underlined by its expected impact in increasing efficiency of discovery pipelines, the development of more economic and eco-friendly end-products and finally in contributing to the implementation of the objectives of the EU Blue Growth.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: NMP-10-2014 | Award Amount: 8.00M | Year: 2015

The key therapeutic issue in diabetes mellitus type I and II is glycaemic control. Reductions of constant self-control, of insulin injections, and of long-term complications would have tremendous benefit for quality of life. The best therapy option is the transplantation of allogeneic islet cells, but the current state of the art limits the applicability of this approach. Implanting unprotected grafts requires lifelong administration of immunosuppressants, and protecting the cells against adverse immune reactions by current encapsulation strategies reduces their functionality and survival to an extend that makes frequent refresher implantations necessary. Currently, a maximum of 2 years glycaemia regulation has been shown for the encapsulated approach. In BIOCAPAN, bringing experts from different fields all together, we aim at developing an innovative treatment, based on the implantation of allogeneic islet cells that are embedded in a complex microcapsule. We will design a GMP-grade bioactive microcapsule that will maximize the long-term functionality and survival of pancreatic islets by prevention of pericapsular fibrotic overgrowth, in situ oxygenation, innovative extracellular matrix microenvironment reconstruction and immune-system modulation. We will establish a GMP-grade microfluidic microencapsulation platform to protect freshly harvested islets quickly in a standardized and reproducible way. We aim for full preclinical validation and we will establish a complete protocol in accordance with the provisions of the Advanced Therapy Medicinal Products Regulation, in order to start clinical trials within one year after the end of the project. We aim for 5-years insulin injection free treatment, without immunosuppressants, which would tremendously benefit diabetes mellitus patients who require insulin (all Type I and about one in six Type II Diabetes Mellitus patients).

Moros M.,University of Zaragoza | Hernaez B.,Instituto Nacional Of Investigacion Y Tecnologia Agraria Y Alimentaria | Garet E.,NanoImmunoTech SL | Dias J.T.,University of Zaragoza | And 6 more authors.
ACS Nano | Year: 2012

Magnetic nanoparticles (NPs) hold great promise for biomedical applications. The core composition and small size of these particles produce superparamagnetic behavior, thus facilitating their use in magnetic resonance imaging and magnetically induced therapeutic hyperthermia. However, the development and control of safe in vivo applications for NPs call for the study of cell-NP interactions and cell viability. Furthermore, as for most biotechnological applications, it is desirable to prevent unspecific cell internalization of these particles. It is also crucial to understand how the surface composition of the NPs affects their internalization capacity. Here, through accurate control over unspecific protein adsorption, size distribution, grafting density, and an extensive physicochemical characterization, we correlated the cytotoxicity and cellular uptake mechanism of 6 nm magnetic NPs coated with several types and various densities of biomolecules, such as glucose, galactose, and poly(ethylene glycol). We found that the density of the grafted molecule was crucial to prevent unspecific uptake of NPs by Vero cells. Surprisingly, the glucose-coated NPs described here showed cellular uptake as a result of lipid raft instead of clathrin-mediated cellular internalization. Moreover, these glucose-functionalized NPs could be one of the first examples of NPs being endocytosed by caveolae that finally end up in the lysosomes. These results reinforce the use of simple carbohydrates as an alternative to PEG molecules for NPs functionalization when cellular uptake is required. © 2012 American Chemical Society.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: NMBP-10-2016 | Award Amount: 6.00M | Year: 2017

Inflammatory bowel diseases (IBD) are the second most common immune-mediated disorders in Europe, affecting more particularly young people. The current therapies, including antibodies, show three main drawbacks: efficacy, tolerability and convenience. NEW DEAL solution will offer radical therapeutic progress for all IBD patients, thanks to the improved efficacy and increased safety of the specific JAK3 inhibition, which has been proven in clinics to be a target of great interest, the better tolerability of siRNA in term of immunogenicity and the good convenience with oral administration. To achieve this challenge, we will address three objectives: i) Specifically inhibit JAK 3 in a highly selective and safer manner by the mean of siRNA carefully designed and validated, ii) Deliver the siRNA therapeutic locally to the inflamed gut, by combining innovative nanostructured lipid carriers enabling their transport across the mucus, the intestinal barrier and the plasma membrane of the target cells, with polymeric capsules for protecting siRNA nanotherapeutics during their transit along the GI tract, thus allowing an oral administration, and iii) Promote the clinical translation and the future industrial transfer of this new clinical product, by addressing manufacturing, safety and efficacy evaluation at the late preclinical stage, to generate a Regulatory Submission Package and a Clinical Development Plan. The NEW DEAL project brings together clinical experts on IBD, leading scientists in nanomedicine, RNAi biology and immunology, innovative SMEs with a strong background in nanosafety, design of capsules and regulatory issues and an established pharma company with historic expertise on gastroenterology medicinal products. If successful, NEW DEAL will open new avenues for siRNA-based therapy in IBD with oral administration.

Olivieri D.N.,University of Vigo | Von Haeften B.,University of Vigo | Sanchez-Espinel C.,Nanoimmunotech SL | Faro J.,University of Vigo | And 4 more authors.
Immunogenetics | Year: 2014

Reptiles and mammals diverged over 300 million years ago, creating two parallel evolutionary lineages amongst terrestrial vertebrates. In reptiles, two main evolutionary lines emerged: one gave rise to Squamata, while the other gave rise to Testudines, Crocodylia, and Aves. In this study, we determined the genomic variable (V) exons from whole genome shotgun sequencing (WGS) data in reptiles corresponding to the three main immunoglobulin (IG) loci and the four main T cell receptor (TR) loci. We show that Squamata lack the TRG and TRD genes, and snakes lack the IGKV genes. In representative species of Testudines and Crocodylia, the seven major IG and TR loci are maintained. As in mammals, genes of the IG loci can be grouped into well-defined IMGT clans through a multi-species phylogenetic analysis. We show that the reptilian IGHV and IGLV genes are distributed amongst the established mammalian clans, while their IGKV genes are found within a single clan, nearly exclusive from the mammalian sequences. The reptilian and mammalian TRAV genes cluster into six common evolutionary clades (since IMGT clans have not been defined for TR). In contrast, the reptilian TRBV genes cluster into three clades, which have few mammalian members. In this locus, the V exon sequences from mammals appear to have undergone different evolutionary diversification processes that occurred outside these shared reptilian clans. These sequences can be obtained in a freely available public repository ( © 2014 Springer-Verlag.

Olivieri D.,University of Vigo | Faro J.,University of Vigo | Faro J.,Instituto Biomedico Of Vigo | Faro J.,Instituto Gulbenkian Of Ciencia | And 4 more authors.
Immunogenetics | Year: 2013

Variable (V) domains of immunoglobulins (Ig) and T cell receptors (TCR) are generated from genomic V gene segments (V-genes). At present, such V-genes have been annotated only within the genome of a few species. We have developed a bioinformatics tool that accelerates the task of identifying functional V-genes from genome datasets. Automated recognition is accomplished by recognizing key V-gene signatures, such as recombination signal sequences, size of the exon region, and position of amino acid motifs within the translated exon. This algorithm also classifies extracted V-genes into either TCR or Ig loci. We describe the implementation of the algorithm and validate its accuracy by comparing V-genes identified from the human and mouse genomes with known V-gene annotations documented and available in public repositories. The advantages and utility of the algorithm are illustrated by using it to identify functional V-genes in the rat genome, where V-gene annotation is still incomplete. This allowed us to perform a comparative human-rodent phylogenetic analysis based on V-genes that supports the hypothesis that distinct evolutionary pressures shape the TCRs and Igs V-gene repertoires. Our program, together with a user graphical interface, is available as open-source software, downloadable at © 2013 Springer-Verlag Berlin Heidelberg.

Agency: European Commission | Branch: H2020 | Program: SME-2 | Phase: SMEInst-02-2016-2017 | Award Amount: 1.93M | Year: 2016

NANOIMMUNOTECH (NIT) is a nanobiotechnology Company which is the sole exploiter of an exclusive ultrasensitive biosensor nanotechnology, called HEATSENS. Thanks to the innovation of using gold nanoprisms, it is able to detect analytes with a low level of detection (attomolar detection limit, one million times more sensitive than competitors), in a faster, cheaper and simpler way than current methodologies do. The aim of this Project is to implement HEATSENS technology in a specific biosensor product: HEATSENS_S, a biosensor able to detect Salmonella in chicken meat on the same working day both for positive and negative results, at an affordable price for customers (where current methodologies take not less than 19hrs). It means a huge impact for the poultry industry, in terms of time and money saved, and food safety. HEATSENS_S is already implemented on a lab prototype (TRL6), and its commercial, technical and financial viability was proved and reported on the SMEI-1 Feasibility study. Relevant final customers (who acknowledge to be willing to pay for the product and collaborated on the product specifications) and key stakeholders, are also involved in the Project. These contacts will be expand during SMEI-2 in order to set a solid commercialisation channel. HEATSENS_S will be market ready in 18 months time, right after the end of the Project. It will be the inflection point in NIT profit, turnover and human resources trends, leading its medium and long term business strategy and increasing NIT Company value up to 30 times, multiplying by 4 their sales from 2019. All in all, once that this first launch is on the market, NIT will easily enter different biosensor market niches by extending HEATSENS_S. The business model consists on a device in which consumables for the detection of different analytes (Tests) must be load. Thus, further Tests launching is forecasted in order to position HEATSENS and NIT at the pole position of the global biosensors market.

Agency: European Commission | Branch: H2020 | Program: SME-1 | Phase: BIOTEC-5a-2014-1 | Award Amount: 71.43K | Year: 2015

NANOIMMUNOTECH (NIT), a leading company in nanobiotechnology with know-how that has been applied to the field of nanobiosensing and especially the agro-food sector introduces HEATSENS in the poultry industry: a solution that transforms into a portable and easy-to-use device with its most cutting-edge know-how in biosensors. HEATSENS is based on a revolutionary nanobiosensing technology owned by the company, whose main characteristics (highly sensitive, rapid detection and simplicity) are the ideal response to a clear need in this sector to test for Salmonella. Salmonella is the second most commonly reported gastrointestinal infection, requiring hospitalisation in many cases, and it can be fatal. One of the most common ways of contracting it is by eating contaminated chicken meat; thus meat companies are required to carry out periodic tests, for which they send samples to specialist laboratories that have a response time of up to 7 days for the analyses, which may mean financial losses. Given that this technology fits into the NIT development strategy, it was decided to perform proofs of concept with several companies in the sector, which clearly showed that HEATSENS_S detects Salmonella at a higher sensitivity in only 3 hours. In light of these results, these potential customers have already shown their keen interest in HEATSENS_S. Now, its conversion into an easy-to-use portable device makes performing in-house testing possible throughout the production chain, providing companies with greater control over product quality and avoiding losses associated with contamination not detected in time, all at a lower cost than current tests today. NIT Management considers this to be the optimum catalyst for the growth of the company and its expansion worldwide and HEATSENS, the flagship product, to make their efforts profitable in nanobiosensing.

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