DestiNA Genomics Ltd.

Edinburgh, United Kingdom

DestiNA Genomics Ltd.

Edinburgh, United Kingdom
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Angelica Luque-Gonzalez M.,University of Granada | Tabraue-Chavez M.,DestiNA Genomica S.L. Parque Tecnologico Ciencias de la Salud PTS | Lopez-Longarela B.,DestiNA Genomica S.L. Parque Tecnologico Ciencias de la Salud PTS | Maria Sanchez-Martin R.,University of Granada | And 7 more authors.
Talanta | Year: 2018

Protozoan parasites of the Trypanosomatidae family can cause devastating diseases in humans and animals, such as Human African Trypanosomiasis or Sleeping Sickness, Chagas disease and Leishmaniasis. Currently, there are molecular assays for detecting parasitic infections and their post-treatment monitoring based on nucleic acid amplification, but there are still certain limitations which limit the development of assays that can detect and discriminate between parasite infections with a single test. Here, we present the development of a novel molecular assay for the rapid identification of Trypanosomatids, integrating DNA analysis by dynamic chemistry in conjunction with Matrix-Assisted Laser Desorption Ionization – Time-of-Flight Mass Spectrometry (MALDI-ToF). Differentiation of Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp. is now possible using a single reaction tube, and enables rapid identification of Trypanosomatids. The test is based on a singleplex PCR, using a specific primer pair that amplifies a 155 base pair segment of the 28S ribosomal RNA gene, within a conserved homology region of Trypanosomatidae species. Amplified fragments are analysed by dynamic chemistry using two abasic PNA probes and the four reactive nucleobases – containing an aldehyde functional group - with MALDI-ToF to identify unique molecular patterns created by each specie due to their single base differences (Single Nucleotide Fingerprint ‘SNF’) in this highly homologous region. This novel assay offers the possibility to expand routine diagnostic testing for Trypanosomatids, and monitoring of therapeutic responses to these infectious diseases. © 2017 Elsevier B.V.


Rissin D.M.,Quanterix | Lopez-Longarela B.,DestiNA Genomics Ltd. | Lopez-Longarela B.,DestiNA Genomica S.L. Parque Tecnologico Ciencias de la Salud PTS | Pernagallo S.,DestiNA Genomics Ltd. | And 9 more authors.
PLoS ONE | Year: 2017

We have developed a single probe method for detecting microRNA from human serum using single molecule arrays, with sequence specificity down to a single base, and without the use of amplification by polymerases. An abasic peptide nucleic acid (PNA) probe - containing a reactive amine instead of a nucleotide at a specific position in the sequence - for detecting a microRNA was conjugated to superparamagnetic beads. These beads were incubated with a sample containing microRNA, a biotinylated reactive nucleobase - containing an aldehyde group - that was complementary to the missing base in the probe sequence, and a reducing agent. When a target molecule with an exact match in sequence hybridized to the capture probe, the reactive nucleobase was covalently attached to the backbone of the probe by a dynamic covalent chemical reaction. Single molecules of the biotin-labeled probe were then labeled with streptavidin-β-galactosidase (SβG), the beads were resuspended in a fluorogenic enzyme substrate, loaded into an array of femtoliter wells, and sealed with oil. The array was imaged fluorescently to determine which beads were associated with single enzymes, and the average number of enzymes per bead was determined. The assay had a limit of detection of 500 fM, approximately 500 times more sensitive than a corresponding analog bead-based assay, with target specificity down to a single base mis-match. This assay was used to measure microRNA-122 (miR-122) - an established biomarker of liver toxicity - extracted from the serum of patients who had acute liver injury due to acetaminophen, and control healthy patients. All patients with liver injury had higher levels of miR-122 in their serum compared to controls, and the concentrations measured correlated well with those determined using RT-qPCR. This approach allows rapid quantification of circulating microRNA with single-based specificity and a limit of quantification suitable for clinical use. © 2017 Rissin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Henke A.,The Queenss Medical Research Institute | Henke A.,University of Cologne | Grace O.C.,The Queenss Medical Research Institute | Grace O.C.,Napier University | And 9 more authors.
PLoS ONE | Year: 2012

Background and Aim: During prostate development, mesenchymal-epithelial interactions regulate organ growth and differentiation. In adult prostate, stromal-epithelial interactions are important for tissue homeostasis and also play a significant role in prostate cancer. In this study we have identified molecules that show a mesenchymal expression pattern in the developing prostate, and one of these showed reduced expression in prostate cancer stroma. Methodology and Principal Findings: Five candidate molecules identified by transcript profiling of developmental prostate mesenchyme were selected using a wholemount in situ hybridisation screen and studied Decorin (Dcn), Semaphorin6D (Sema6D), SPARC/Osteonectin (SPARC), Sprouty1 (Spry-1) and Tsukushi (Tsku). Expression in rat tissues was evaluated using wholemount in situ hybridisation (postnatal day (P) 0.5) and immunohistochemistry (embryonic day (E) E17.5, E19.5; P0.5; P6; 28 & adult). Four candidates (Decorin, SPARC, Spry-1, Tsukushi) were immunolocalised in human foetal prostate (weeks 14, 16, 19) and expression of Decorin was evaluated on a human prostate cancer tissue microarray. In embryonic and perinatal rats Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi were expressed with varying distribution patterns throughout the mesenchyme at E17.5, E19.5, P0.5 and P6.5. In P28 and adult prostates there was either a decrease in the expression (Semaphorin6D) or a switch to epithelial expression of SPARC, and Spry-1, whereas Decorin and Tsukushi were specific to mesenchyme/stroma at all ages. Expression of Decorin, SPARC, Spry-1 and Tsukushi in human foetal prostates paralleled that in rat. Decorin showed mesenchymal and stromal-specific expression at all ages and was further examined in prostate cancer, where stromal expression was significantly reduced compared with non-malignant prostate. Conclusion and Significance: We describe the spatio-temporal expression of Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi in developing prostate and observed similar mesenchymal expression patterns in rat and human. Additionally, Decorin showed reduced expression in prostate cancer stroma compared to non-malignant prostate stroma. © 2012 Henke et al.


Pernagallo S.,DestiNA Genomics Ltd. | Ventimiglia G.,STMicroelectronics | Cavalluzzo C.,DestiNA Genomics Ltd. | Alessi E.,STMicroelectronics | And 3 more authors.
Sensors (Switzerland) | Year: 2012

This manuscript describes the use of a novel biochip platform for the rapid analysis/identification of nucleic acids, including DNA and microRNAs, with very high specificity. This approach combines a unique dynamic chemistry approach for nucleic acid testing and analysis developed by DestiNA Genomics with the STMicroelectronics In-Check platform, which comprises two microfluidic optimized and independent PCR reaction chambers, and a sequential microarray area for nucleic acid capture and identification by fluorescence. With its compact bench-top "footprint" requiring only a single technician to operate, the biochip system promises to transform and expand routine clinical diagnostic testing and screening for genetic diseases, cancers, drug toxicology and heart disease, as well as employment in the emerging companion diagnostics market. © 2012 by the authors; licensee MDPI, Basel, Switzerland.


Venkateswaran S.,University of Edinburgh | Luque-Gonzalez M.A.,University of Granada | Tabraue-Chavez M.,DestiNA Genomica S.L. Parque Tecnologico Ciencias de la Salud PTS | Fara M.A.,DestiNA Genomica S.L. Parque Tecnologico Ciencias de la Salud PTS | And 11 more authors.
Talanta | Year: 2016

Over the last decade, circulating microRNAs have received attention as diagnostic and prognostic biomarkers. In particular, microRNA122 has been demonstrated to be an early and more sensitive indicator of drug-induced liver injury than the widely used biomarkers such as alanine aminotransferase and aspartate aminotransferase. Recently, microRNA122 has been used in vitro to assess the cellular toxicity of new drugs and as a biomarker for the development of a rapid test for drug overdose/liver damage. In this proof-of-concept study, we report a PCR-free and label-free detection method that has a limit of detection (3 standard deviations) of 15 fmoles of microRNA122, by integrating a dynamic chemical approach for “Single Nucleobase Labelling” with a bead-based platform (Luminex®) thereby, in principle, demonstrating the exciting prospect of rapid and accurate profiling of any microRNAs related to diseases and toxicology. © 2016 Elsevier B.V.


Cavalluzzo C.,Catholic University of Leuven | Cavalluzzo C.,DestiNA Genomics Ltd | Christ F.,Catholic University of Leuven | Voet A.,Catholic University of Leuven | And 9 more authors.
Journal of Peptide Science | Year: 2013

The integration of the viral DNA into the host genome is one of the essential steps in the HIV replication cycle. This process is mediated by the viral enzyme integrase (IN) and lens epithelium-derived growth factor (LEDGF/p75). LEDGF/p75 has been identified as a crucial cellular co-factor of integration that acts by tethering IN to the cellular chromatin. Recently, circular peptides were identified that bind to the C-terminal domain of IN and disrupt the interaction with LEDGF/p75. Starting from the circular peptides, we identified a short peptidic sequence able to inhibit the LEDGF/p75-IN interaction at low μM concentration through its binding to the IN binding site of LEDGF/p75. This discovery can lead to the synthesis of peptidomimetics with high anti-HIV activity targeting the cellular co-factor LEDGF/p75 and not the viral protein IN. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.


Grant
Agency: GTR | Branch: Innovate UK | Program: | Phase: Feasibility Study | Award Amount: 24.75K | Year: 2011

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.


Grant
Agency: GTR | Branch: Innovate UK | Program: | Phase: Feasibility Study | Award Amount: 24.75K | Year: 2012

The objective of this study is the development of a rapid and cheap multiplexed assay to screen milk prior to processing. This will facilitate the identification of contaminated milk, infected herds and individual animals. The project is innovative in that it will apply novel chemical based nucleic acid detection technology to the identification of bacterial pathogens causing mastitis in dairy cattle. This will be achieved without the use of bacterial culture or PCR which are time consuming and expensive respectively. Our test will be run in under two hours without the use of nucleic acid processing enzymes. This feasibility study is based on customer desire for a superior assay to current practice. The resulting assay is expected to have immediates sales opportunities and will have global potential.


Grant
Agency: GTR | Branch: Innovate UK | Program: | Phase: Feasibility Study | Award Amount: 24.63K | Year: 2011

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.


PubMed | DestiNA Genomics Ltd.
Type: Journal Article | Journal: Sensors (Basel, Switzerland) | Year: 2012

This manuscript describes the use of a novel biochip platform for the rapid analysis/identification of nucleic acids, including DNA and microRNAs, with very high specificity. This approach combines a unique dynamic chemistry approach for nucleic acid testing and analysis developed by DestiNA Genomics with the STMicroelectronics In-Check platform, which comprises two microfluidic optimized and independent PCR reaction chambers, and a sequential microarray area for nucleic acid capture and identification by fluorescence. With its compact bench-top footprint requiring only a single technician to operate, the biochip system promises to transform and expand routine clinical diagnostic testing and screening for genetic diseases, cancers, drug toxicology and heart disease, as well as employment in the emerging companion diagnostics market.

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