Liquid biopsy is likely to play an increasing role in identifying patients with colorectal cancer (CRC) who are likely to relapse after surgery, and has potential for optimising treatment for individual patients, according to new research.
Of 805 patients in the phase III IDEA-FRANCE trial who had liquid biopsy prior to adjuvant chemotherapy for stage III CRC, 109 (13.5%) had circulating tumour DNA (ctDNA) in their blood.
In this group, two-year disease-free survival (DFS) was 64%, compared to 82% in those who were ctDNA negative.
“In this large prospective trial, we confirmed that ctDNA is an independent prognostic factor in colorectal cancer and that approximately six out of 10 patients who are ctDNA positive will remain disease-free two years after standard adjuvant chemotherapy, compared to eight out of 10 of those who are ctDNA negative,” said study author Prof Julien Taieb, Hôpital European Georges Pompidou, Paris, France.
IDEA-FRANCE also showed that six months of adjuvant treatment was superior to three months in both ctDNA positive and negative patients, and that ctDNA positive patients treated for six months had a similar prognosis to ctDNA negative patients treated for three months.
Adjuvant therapy was FOLFOX (folinic acid, fluorouracil and oxaliplatin) in 90% of cases.
“ctDNA testing did not predict which patients should have three or six months of adjuvant chemotherapy and there is continuing debate over the optimal type and duration of treatment for patients who are ctDNA positive, but we do now know that ctDNA is a major prognostic factor which will be very useful in stratifying patients and driving future trials of colorectal cancer,” said Taieb.
“In all subgroups, ctDNA positive patients who only had three months of adjuvant therapy had the worst prognosis,” he added.
Thirty to 50% of patients with localised CRC relapse despite primary optimal therapy, and a second study reported at the ESMO Congress 2019 investigated whether ctDNA can be used to detect minimal residual disease and identify those at risk of recurrence.
The results showed that post-surgical plasma ctDNA predicted metastatic relapse a median of 10 months before recurrence was visible on radiological scans (hazard ratio 11.33; p=0.0001).
The researchers concluded that plasma ctDNA testing opens up an opportunity for precision treatment of patients with localised CRC.
Commenting on the results of the CRC presentations, Prof Alberto Bardelli, University of Turin, Italy, said: “When patients have surgery for early stage colorectal cancer, doubts remain as to whether the disease has been completely eradicated and, as a result, patients often receive adjuvant chemotherapy. However, the IDEA-FRANCE results have shown we can now use a blood test to say whether the patient is clear or not.”
ecancerecancer.org/en/news/16682-esmo-2019-liquid-biopsy-has-prognostic-role-in-colorectal-cancer-and-potential-for-guiding-therapy
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by Prof. Michael Vogeser, Dr Judy Stone and Prof. Alan Rockwood While analytical standardization and metrological traceability are well-defined terms, ‘methodological standardization’ in clinical mass spectrometry is still in a developing stage. We propose a framework that facilitates the widespread implementation of this highly complex and very powerful technology and is based on two pillars – standardization of the description of LC-MS/MS methods and standardization of the release of clinical test results as a three-step sequence of method validation, batch validation and validation of individual measurements. Mass spectrometry in the clinical laboratory Mass spectrometry (MS)-based methods now play an important role in many clinical laboratories worldwide. To date, areas of application have focused especially on screening for hereditary metabolic diseases, therapeutic drug monitoring, clinical toxicology and endocrinology. In fact, these techniques offer significant advantages over immunoassays and photometry as basic standard technologies in clinical chemistry: high analytical selectivity through true molecular detection; wide range of applications without the need for specific molecular features (as in UV detection or specific epitopes); high multiplexing capacity and information-rich detection; and, in many cases, matrixindependent analyses, thanks to the principle of isotope dilution [1].
Various MS technologies – in particular tandem MS (MS/MS-coupling with molecular fragmentation), time-of-flight (TOF) MS and Orbitrap-MS – with front-end fractionation technologies such as HPLC or UPLC potentially allow very reliable analysis, but the technology itself is no guarantee of this: these techniques have a very high complexity and a wide range of potential sources of error [2] which require comprehensive quality assurance [3–5]. Indeed, the high degree of complexity is still the main hurdle for the application of MS in the special environment of clinical laboratories. Specific challenges of this type of laboratory – in contrast to research and development laboratories – include: heterogeneous mix of staff qualifications; requirement for maximum handling safety when operating a large number of analysis platforms; work around the clock; and direct impact on the outcome of the individual patient.
Indeed, after more than two decades of commercial availability of LC-MS/MS instruments, their application in a global perspective has remained very limited. The translation of MS into fully automated ‘black box’ instruments is underway, but still far from being realized on a large scale [6], with laboratory developed tests (LDTs) still dominating the field of clinical MS applications. Kit solutions for specific analytes provided by the in vitro diagnostics (IVD) industry are becoming increasingly available, but their application also requires a very high level of skills and competence from laboratories.
Two main differences of MS-based LDTs as opposed to standard ‘plug-and-play’ analysis systems in today’s clinical laboratories can be identified: first, the high heterogeneity of device configurations and second, the handling of large amounts of data, from sample list structures to technical metadata analysis.
In fact, the random access working mode is now so widespread in all clinical laboratories that the ‘analytical batch’ is no longer standard in laboratories. In the same way, modern analytical instruments no longer challenge the end users with extensive metadata (such as reaction kinetics or calibration diagrams). To achieve the goal of making the extraordinary and disruptive analytical power of MS fully usable for medicine to an appropriate extent, approaches to master the heterogeneity of platform configurations and to regulate the handling of batches and metadata are urgently needed – and standardization efforts seem to be crucial in this context. Standardization of the method description IVD companies manufacture many different instrument platforms, but each of these platforms is very homogeneous worldwide and is produced in large quantities for years. In contrast, MS platforms in clinical laboratories have to be individually assembled from a very large number of components from many manufacturers (sample preparation modules, autosamplers, high performance pumps, switching valves, chromatography columns, ion sources, mass analysers, vacuum systems, software packages, etc). As a result, hardly any two instrument configurations in different laboratories correspond completely with each other. This makes handling very demanding for operators, maintenance personnel, and service engineers.
Methods implemented on these heterogeneous platforms (e.g. instruments from various vendors) are in turn characterized by a very considerable number of variables, e.g. chromatographic gradients, labelling patterns of internal standards, purity of solvents, dead volume of flow paths, etc.
Taken together, the variety of assays referring to an identical analyte (such as tacrolimus or testosterone) is enormous, with an almost astronomical combinatorial complexity.
However, method publications are still traditionally written more or less in a case report approach: the feasibility and performance of a method realization is demonstrated for one individual system configuration. It is usually not clear which features are really essential for the method and which features can be variable between different implementations – and which second implementation can still be considered ‘the same’ method. This means that the question of the true ‘identity’ of a method has not yet been deepened by application notes or publications in scientific journals; thus the level of abstraction required here is missing.
In an attempt to standardize the description of MS/MS-based methods, we selected a set of 35 characteristics that are defined as essential for a method (see Table 1) [7], for example, main approach of sample preparation (e.g. protein precipitation with acetonitrile), main technique of ionization (e.g. electrospray ionization in negative mode); molecular structure of the internal standard; mass transitions; calibration range. In addition, we define 15 characteristics of a method that cannot or should not be realistically standardized in time and space (examples: manufacturer and brand of the MS detector; dead volume of the flow path; lot of analytical columns and solvents). These characteristics – identified as variable – should be documented in the internal report files.
We found it feasible to describe several exemplary MS/MS methods using this scheme and a corresponding matrix. On the basis of this matrix, the method transfer to different platforms and laboratories will be much easier and more reliable. Specifying the identity of a method in the proposed way has the essential advantage that a method revalidation can be transparently triggered by defined criteria, e.g. the use of a novel internal standard with a different labelling pattern.
The proposed scheme for method description may also be the basis of a comprehensive traceability report for any result obtained by an MS-based method in the clinical laboratory. Standardization of batch release (Table 2) While today’s routine analyser platforms essentially provide unambiguous final results for each sample, the process of generating quantitative results from primary data in MS is open and transparent. Primary data in MS are the peak areas of the target analyte observed in diagnostic samples. In addition to these primary data, a range of metadata is provided (e.g. internal standard area, peak height-to-area, peak skewness, qualifier peak area; metadata related to analytical batches, e.g. coefficient of variation (CV) of internal standard areas). This transparency and abundance of data is a cornerstone of the high potential reliability of MS-based assays and therefore their interpretation is very important [8, 9].
However, the evaluation of this metadata – related to individual samples and batches – is nowadays done very heterogeneously from laboratory to laboratory [10]; this applies to LDTs as well as to commercially available kit products. The structure of analytical batches is also very variable and there is no generally accepted standard (number and sequence of analysis of calibration samples in relation to patient and quality control samples, blank injections, zero samples, etc).
While the validation of methods – which is performed before a method is introduced into the diagnostic routine – is discussed in detail in the literature (and in practice), the procedures applied to primary data before release for laboratory reporting have not yet been standardized. Validation is generally defined as the process of testing whether predefined performance specifications are met. Therefore, quality control and release of analytical batches and patient results should also be considered a process of validation, and criteria for the acceptance or rejection of results should be predefined.
A three-step approach to validation, covering the entire life cycle of methods in the clinical laboratory, can be conceptualized: dynamic validation should integrate validation of methods, validation of analytical batches and validation of individual test readings. We believe that standardization of this process of batch and sample result validation and release is needed as a guide for developers of methods, medical directors, and technicians.
In a recent article published in Clinical Mass Spectrometry [11], we propose a list of characteristics that should be considered for batch and sample release. In this article we only mention figures for merits and issues to be addressed and do not claim to have specific numerical acceptance criteria. Therefore, this generic list of items is intended as a framework for the development of an individual series and batch validation plan in a laboratory. Furthermore, we consider this list to be a living document, subject to further development and standardization as the field matures.
We believe that it is essential to include basic batch and sample release requirements as essential characteristics in the description of a method [7]. Therefore, we believe that efforts to standardize method description and batch/sample release should be synergistically linked to facilitate the use of MS in routine laboratories.
The approach proposed to clinical MS in these two companion articles [7, 11] can be the basis for discussion and eventually for the development of official standards for these areas by the Clinical and Laboratory Standards Institute (CLSI) and/or International Organization for Standardization (ISO). We believe that these documents can provide a solid basis for internal and external audits of LC-MS/MS-based Quality Control April/May 2020 9 | LDTs, which will become particularly relevant in the context of the IVD Regulation 746 in the European Union [12].
Both approaches – standardized description of MS methods and standardization of batch release – aim at implementing methodological traceability. This corresponds to the analytical standardization and metrological traceability of measurements to higher order reference materials [13, 14]. Future perspectives In the future, a commercialization of MS-based black-box instruments on a larger scale is expected. However, LC-MS/MS will remain a critical technique for LDTs, and the flexibility of MS to develop tests on demand – independent of the IVD industry on fully open LC-MS/MS platforms – will remain a key pillar of laboratory medicine.
Both publications, which this article puts into context [7, 11], have been published in Clinical Mass Spectrometry, the first and only international journal dedicated to the application of MS methods in diagnostic tests including publications on best practice documents. Both articles are freely available.
Clinical Mass Spectrometry is the official journal of MSACL (The Association for Mass Spectrometry: Applications to the Clinical Laboratory; www.msacl.org). MSACL organizes state-of-the-art congresses that focus on translating MS from clinical research to diagnostic tests (i.e. bench to clinic).
In summary, we advocate innovative approaches to methodological standardization of LC-MS/MS methods to master the complexity of this powerful technology and to facilitate and promote its safe application in clinical laboratories worldwide. The authors Michael Vogeser*1 MD, Judy Stone2 PhD, Alan Rockwood3 PhD 1 Hospital of the University of Munich (LMU), Institute of Laboratory Medicine, Munich, Germany University of California, San Francisco Medical Center, Laboratory Medicine, Parnassus Chemistry, San Francisco, CA, USA 3 Rockwood Scientific Consulting, Salt Lake City, UT, USA
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New insights into how the colon functions and actually expels its contents have been revealed for the first time following decades of study by Flinders University researchers.
It promises new diagnostics tools and treatments for gastrointestinal disorders to address problems with bowel movements leading to constipation, diarrhoea and pain, affecting hundreds of millions of people worldwide.
Propulsion of intestinal contents is controlled by millions of neurons within the wall of the gut, known as the enteric nervous system. Capable of operating independently of the brain, a functioning enteric nervous system is essential for life – but exactly how it functions has been a mystery.
By unravelling the neural circuits of the enteric nervous system in guinea pigs and humans Professor Marcello Costa and colleagues are able to understand how the enteric nervous system ensures that food is slowly mixed and propelled along the digestive tube, allowing for absorption of nutrients and excretion of waste.
“For the first time we have combined video recording intestinal movements with a pressure-measuring manometric probe, enabling movements, pressures and electrical activities to be recorded all at the same time within the colon.
“This powerful combination of techniques applied to a guinea pig colon identified several distinct neural mechanisms involved in the propulsion of colonic contents.
“This answers the deceptively simple question of how neural mechanisms within the colon manage the propulsion of bowel contents” Professor Costa says.
“The findings also show how studies in human and animals can be complementary, identifying fundamental mechanisms that are shared across species – in this case guinea pigs and humans. “Currently we treat intestinal disorders by addressing the symptoms, such a stopping-up diarrhoea or softening stools to ease constipation, but as a result of this new understanding of the neural networks of the enteric system, clinicians may be able to develop treatments that treat the cause of the problems” Professor Costa says.
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Japanese scientists report a new method to construct 3D models from 2D images. The approach, which involves non-rigid registration with a blending of rigid transforms, overcomes several of the limitations in current methods. The researchers validate their method by applying it to the Kyoto Collection of Human Embryos and Fetuses, the largest collection of human embryos in the world, with over 45,000 specimens.
MRI and CT scans are standard techniques for acquiring 3D images of the body. These modalities can trace with unprecedented precision the location of an injury or stroke. They can even reveal the microscopic protein deposits seen in brain pathologies like Alzheimer’s disease. However, for the best resolution, scientists still depend on slices of the specimen, which is why cancer and other biopsies are taken. Once the information desired is acquired, scientists use algorithms that can put together the 2D slices to recreate a simulated 3D image. In this way, they can reconstruct an entire organ or even organism.
Stacking slices together to create a 3D image is akin to putting a cake together after it has been cut. Yes, the general shape is there, but the knife will cause certain slices to break so that the reconstructed cake never looks as beautiful as the original. While this might not upset the party of five-year olds who want to indulge, the party of surgeons looking for the precise location of a tumour are harder to appease.
“The sectioning process stretches, bends and tears the tissue. The staining process varies between samples. And the fixation process causes tissue destruction,” explains Nara Institute of Science and Technology (NAIST), Nara, Japan, Associate Professor Takuya Funatomi, who led the project. Fundamentally, there are three challenges that emerge with the 3D reconstruction. First is non-rigid deformation, in which the position and orientation of various points in the original specimen have changed. Second is tissue discontinuity, where gaps may appear in the reconstruction if the registration fails. Finally, there is a scale change, where portions of the reconstruction are disproportional to their real size due to non-rigid registration.
For each of these problems, Associate Professor Takuya Funatomi and his research team proposed a solution that when combined resulted in a reconstruction that minimizes all three factors using less computational cost than standard methods.
“First, we represent non-rigid deformation using a small number of control points by blending rigid transforms,” says Funatomi. The small number of control points can be estimated robustly against the staining variation.
“Then we select the target images according to the non-rigid registration results and apply scale adjustment,” he continues.
The new method mainly focuses on a number of serial section images of human embryos from the Kyoto Collection of Human Embryos and Fetuses and could reconstruct 3D embryos with extraordinary success.
Notably, there are no MRI or CT scans of the samples, meaning no 3D models could be used as a reference for the 3D reconstruction. Further, wide variability in tissue damage and staining complicated the reconstruction.
Nara Institute of Science and Technology
https://tinyurl.com/y4ealgow
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The Netherlands-based Pharming Group, a specialty pharmaceutical company, have seen encouraging results from it RUCONEST (recombinant human C1 inhibitor) treatment in patients with confirmed COVID-19 infections. The patients were treated under a compassionate use program at the University Hospital Basel, Switzerland.
Dr. Michael Osthoff, University Hospital Basel, Switzerland and the treating physician, said: “Although this is an uncontrolled, small treatment experience, the results demonstrate the potential effectiveness of using RUCONEST as an anti-inflammatory approach to inhibit the complement and contact systems after SARS-CoV-2 infection.”
Four male patients and one female patient (between 53-85 years of age) with COVID-19 and suffering from related severe pneumonia, who did not improve despite standard treatment, including hydroxychloroquine and lopinavir/ritonavir, were administered RUCONEST at an initial dose of 8400 U, followed by 4200 U every 12 hours for three additional doses. No allergic reactions or drug related adverse events were reported.
Following treatment with RUCONEST, fever resolved in four of the five patients within 48 hours, and laboratory markers of inflammation decreased significantly (CRP, IL-6). Soon thereafter, the patients were discharged from the hospital as fully recovered. One patient had increased oxygen requirement and was temporarily transferred to the ICU for intubation, but over the subsequent days recovered and was released from the ICU.
Following these initial results, a multinational, randomized, controlled, investigator-initiated clinical trial with up to 150 patients with confirmed COVID-19 infections, requiring hospitalisation due to significant COVID-19 related symptoms is planned. The study will be led by Dr. Osthoff.
RUCONEST® is commercialised by Pharming in the US and in Europe, and the company holds all other commercialisation rights in other countries not specified below. In some of these other countries distribution is made in association with the HAEi Global Access Program (GAP). RUCONEST is distributed in Argentina, Colombia, Costa Rica, the Dominican Republic, Panama, and Venezuela by Cytobioteck, in South Korea by HyupJin Corporation and in Israel by Kamada.
Pharming’s technology platform includes a unique production process that has proven capable of producing industrial quantities of pure high quality recombinant human proteins in a more economical and less immunogenic way compared with current cell-line based methods.
Astell Scientific is a world renowned manufacturer and supplier of steam sterilizers. Astell Scientific autoclaves, steam generators and effluent decontamination systems (EDS) are designed to meet the exacting demands of modern Laboratory, Research and Medical professionals, and as such incorporate innovations such as colour touchscreen controllers as standard throughout the range.
We manufacture: • Circular section autoclaves from 30-330 litres • Square Section autoclaves from 125 – 2000 litres • Steam Generators up to 72 kW • Effluent Decontamination Systems (EDS) • Customized steam sterilizers to meet the most challenging of applications
All Astell autoclaves are manufactured in accordance with standards and directives including ISO 9001:2015, Pressure Equipment Directive (PED 2014/68/EU) and CE (Conformité Européenne).www.astell.com
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Avacta Group, the developer of Affimer biotherapeutics and reagents, has entered into a collaboration with Integumen to evaluate recently generated Affimer reagents that bind the SARS-COV-2 spike protein for the detection of the coronavirus in waste water, to provide a real-time alert system to warn of localised COVID-19 outbreaks.
Over 60 percent of COVID-19 positive patients had gastrointestinal symptoms, such as diarrhoea, nausea and vomiting, and the SARS-COV-2 virus was found in their faecal samples. Sampling waste water from households may therefore provide an early warning system for localised outbreaks in communities.
Recently, Avacta announced that it had generated a number of highly specific Affimer reagents that detect the SARS-COV-2 virus spike protein for use in diagnostic tests and in neutralising therapies.
The collaboration with Integumen, announced 13 July, aims to evaluate some of these Affimer reagents in next-generation sensors, based on the real-time bacteria detection and alert system1 developed by Rinocloud, a subsidiary of Integumen, with the aim of integrating these sensors into Modern Water’s Microtox water contamination system to detect the coronavirus. The award-winning Microtox system, which can detect the presence of contaminating bacteria, virus and toxins, is distributed by Modern Water and has a global footprint of over 3,000 installations. The proposed Affimer sensors would be consumable items to be replaced on a roughly monthly basis.
Once initial testing of the Affimer reagents is completed over the next few weeks, validation of the sensors will be carried out using SARS-COV-2 virus samples in a containment level 3 laboratory at the University of Aberdeen. Upon successful completion of this evaluation, Integumen and Avacta will enter into a supply agreement to allow Integumen to manufacture and commercialise the waste water detection sensors globally by retrofitting into Microtox systems.
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Epigenetics company Base Genomics has launched with a team of leading scientists and clinicians with the aim of setting a new gold standard in DNA methylation detection. The company has closed an oversubscribed seed funding round of US$11 million to accelerate development of its TAPS technology, initially focusing on developing a blood test for early-stage cancer and minimal residual disease. The funding round was led by Oxford Sciences Innovation.
DNA methylation is an epigenetic mechanism involved in gene regulation and has been shown to be one of the most promising biomarkers for detecting cancer through liquid biopsy. The existing industry standard for mapping DNA methylation degrades DNA and reduces sequence complexity, however, limiting scientific discovery and clinical sensitivity. Base Genomics’ new technology, TAPS, overcomes these issues and generates significantly more information from a given sample, creating new opportunities in research and clinical application.
Dr Anna Schuh, CMO, Base Genomics, commented: “In order to realize the potential of liquid biopsies for clinically meaningful diagnosis and monitoring, sensitive detection and precise quantification of circulating tumour DNA is paramount. Current approaches are not fit for purpose to achieve this, but Base Genomics has developed a game-changing technology which has the potential to make the sensitivity of liquid biopsies a problem of the past.”
First developed at Ludwig Institute for Cancer Research Branch at the University of Oxford, TAPS is a novel chemical reaction that converts methylated cytosine to thymine under mild conditions. Unlike the industry standard technology, bisulfite sequencing, TAPS does not degrade DNA, meaning that significantly more DNA is available for sequencing. TAPS also better retains sequence complexity, cutting sequencing costs in half and enabling simultaneous epigenetic and genetic analysis.
Dr Vincent Smith, CTO, Base Genomics said: “[TAPS] has the potential to have an impact on epigenetics similar to that which Illumina’s SBS chemistry had on Next Generation Sequencing.”
Base Genomics is led by a highly experienced team of scientists and clinicians, including Dr Smith, a world-leader in genomic product development and former Illumina VP; Dr Schuh, Head of Molecular Diagnostics at the University of Oxford and Principal Investigator on over 30 clinical trials; Drs Chunxiao Song and Yibin Liu, co-inventors of TAPS at the Ludwig Institute for Cancer Research, Oxford; and Oliver Waterhouse, previously an Entrepreneur in Residence at Oxford Sciences Innovation and founding team member at Zinc VC.
Waterhouse, founder and CEO, Base Genomics, said: “The ability to sequence a large amount of high-quality epigenetic information from a simple blood test could unlock a new era of preventative medicine. In the future, individuals will not just be sequenced once to determine their largely static genetic code, but will be sequenced repeatedly over time to track dynamic epigenetic changes caused by age, lifestyle, and disease.”
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OXGENE and The Native Antigen Company are collaborating to scale up production of SARS-CoV-2 reagents by combining OXGENE’s proprietary Adenoviral Protein Machine Technology with The Native Antigen Company’s antigen development expertise. Together, they aim to scale their antigen manufacturing capabilities to deliver high-purity, recombinant proteins for the development of diagnostics and vaccines.
Unlike the PCR tests that are currently being used, these diagnostics will be able to confirm past infections and determine levels of immunity to SARS-CoV-2. This could be invaluable for disease modelling and public health policy, as true transmission rates and case fatality rates can be determined. These tests could also be instrumental for the diagnosis of healthcare workers who have been exposed to the virus to ensure that they have developed natural immunity before returning to work, and to help measure patient immune responses for the rapid development of a SARS-CoV-2 vaccine.
The Native Antigen Company was one of the first recognised suppliers of SARS-CoV-2 antigens in February 2020, demonstrating their ability to rapidly support the diagnostic and vaccine industries with high-quality infectious disease reagents.
OXGENE’s Protein Machine Technology allows for the scalable production of viral proteins in mammalian cells using their proprietary adenoviral expression vector. Through genetic modification, the adenovirus is ‘tricked’ into making SARS-CoV-2 proteins rather than its own, thereby harnessing the innate power of highly scalable viral protein production.
Commenting on the collaboration, Dr Ryan Cawood, Chief Executive, OXGENE, said: “Our novel Protein Machine Technology represents a significant development in the rapid and scalable generation of high-quality viral proteins. We’re delighted that by collaborating with The Native Antigen Company, we can take advantage of our technology to support the needs of researchers racing to develop much-needed diagnostics and vaccines against COVID-19.”
The Native Antigen Company’s recombinant SARS-CoV-2 antigens are produced in mammalian cells to ensure full glycosylation and proper protein folding, both of which are essential for full biological and antigenic activity. The rapid scale up production of SARS-CoV-2 antigens is critical for the development of widely available diagnostic tests.
Dr Andy Lane, Commercial Director, The Native Antigen Company, said: “We are committed to developing the highest-quality reagents in rapid response to emerging epidemic diseases. Since the start of the crisis, the demand for our COVID-19 antigens has increased significantly, and by scaling up production of these vital reagents in collaboration with OXGENE, we hope to be able to support more researchers in their critical work developing diagnostics and vaccines.”
This collaboration builds on a long-standing collegiate relationship between the two Oxford-based businesses as they work towards developing more scalable technologies for the diagnosis of disease, and the cost-effective manufacture of high-quality diagnostics and vaccines.
OXGENE and The Native Antigen Company aim to complete the first validation of this new paradigm in protein expression by May 2020, which could have a demonstrable impact on the race to develop diagnostic kits and vaccines against this virus.
For further information about The Native Antigen Company’s Coronavirus Antigens, visit: https://thenativeantigencompany.com/coronavirus-dashboard/
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Modern science and data sharing converged to underpin a study led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, that identified a gene associated with a rare condition that results in physical and intellectual disabilities of children.
The results suggest that rare variants in the gene DDX6 are associated with a significant disruption in the development of the central nervous system, governing such basic skills as the ability to walk and talk.
“One of the most powerful revelations of this study is the identification of pathogenic mutations in DDX6; a gene not previously linked to childhood disorders and one which appears to play a key role in early brain development,” said Chris Balak, a research associate in TGen’s Neurogenomics Division, and the study’s lead author.
Balak zeroed in on DDX6 by comparing the sequencing results from a 5-year-old Arizona girl who was seen at TGen’s Center for Rare Childhood Disorders (the Center) with those identified in large population databases and to the genomes of her parents, who are healthy. Following this revelation, and preliminary findings posted on a website shared by investigators worldwide, TGen identified four similar cases: two in the U.S., and one each in France and the Netherlands.
These children’s conditions were characterized by intellectual disability, developmental delay, speech and feeding difficulties, low muscle strength with difficulties walking, mild-to-moderate cardiac anomalies, and specific facial features.
“Something we are quite proud of with this work is our combined effort with other physi- cians and scientists in Europe to demonstrate that changes in this gene cause this rare syndrome in multiple patients,” said Dr. Matt Huentelman, TGen Professor of Neruogenomics, Scientific Director of the Center, and one of the study’s senior authors. “Collectively, our clinical and laboratory data describe a new brain development syndrome caused by genetic changes in DDX6.”
TGenwww.tgen.org/news/2019/august/15/tgen-identifies-ddx6-linked-to-disabilities/
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We also use various external services such as Google Webfonts, Google Maps and external video providers. Since these providers may collect personal data such as your IP address, you can block them here. Please note that this may significantly reduce the functionality and appearance of our site. Changes will only be effective once you reload the page
Google Webfont Settings:
Google Maps Settings:
Google reCaptcha settings:
Vimeo and Youtube videos embedding:
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Privacy Beleid
U kunt meer lezen over onze cookies en privacy-instellingen op onze Privacybeleid-pagina.