“Hairclip” protein mechanism explained
Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for biotechnology and medicine.
The shape of a protein determines its function, for example whether it is able to interact with another protein or with a drug. But a protein’s shape is not constant – it may change in response to different conditions, or simply as a matter of course. Understanding how this process works is key to figuring out how to manipulate proteins, for example in order to disrupt a disease. Today’s finding provides important clues that will help focus future research.
The team looked at a family of bacterial RNA-binding proteins that control a basic process in metabolism: one type of bacteria lives in very high temperatures, and the other likes things colder. The goal was to determine how a protein morphs from an active configuration (one that lets it bind to RNA) to an inactive one in two very different environments.
“The process is controlled by mutations, but these mutations aren’t in an obvious place, where the binding happens,” explains Sarah Teichmann, research group leader at the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI) and the Wellcome Trust Sanger Institute. “They’re actually working from a distance, indirectly, to change the shape of those sites. We wanted to know how that works at an atomic level.”
Undertaken initially as a purely computational study, lead author Tina Perica stepped away from her laptop and into the lab, where she worked with others to fill in the picture with experiments in biophysics, and integrated structural biology to detail how these mutations work.
“Any stable protein will have a lot of constraints on its mutational pathways,” says Tina. “These mutations have very few options – just like a person walking along a cliff will need to keep to a narrow path. But at the same time, proteins need enough wiggle room to be able to bind to things, like another protein or a drug. To find where the protein could provide that wiggle room, we retraced its steps millions of years into the past, and used a lot of different approaches to figure out what was happening.”
“If you know how a species of bacteria has evolved, you can reconstruct proteins that it may have had in the past, but which don’t exist today,” says Yasushi Kondo from MRC Laboratory of Molecular Biology. “We made a couple of these proteins, and used X-ray crystallography to solve their structures. That let us see details we would never have seen if we’d only studied proteins from the bacteria that live today. When we put that new information together with computational work and simulations, we started to see a clear picture of how these proteins change.”
“We were really pleased to do the elastic network modelling for this study, because it helps you see the dynamics of how the protein goes from one configuration to another,” says Nathalie Reuters of the University of Bergen, Norway. “It also shows that these fluctuations are the same for natural mutations between the thermophilic and mesophilic organism, for allosteric ligands, for small molecules binding, or for engineered mutations.”
“These proteins provide a very good example of a fundamental biophysical phenomenon that we think can happen in many proteins, regardless of which organism,” says Sarah. “We believe our findings will help future research into manipulating proteins, which has potential applications across the life sciences.”
Perica, T., Kondo, Y, Tiwari, S.P., et al. (2014). Evolution of oligomeric state through allosteric pathways that mimic ligand binding. Science (in press). Published online 19 December 2014; doi:http://dx.doi.org/10.1126/science.1254346
3D Vaccine spontaneously assembles to pack a powerful punch against cancer, infectious diseases
Vaccine delayed tumor growth in mice
NIBIB-funded researchers have developed a novel 3D vaccine that could provide a more effective way to harness the immune system to fight cancer as well as infectious diseases. The vaccine spontaneously assembles into a scaffold once injected under the skin and is capable of recruiting, housing, and manipulating immune cells to generate a powerful immune response. The vaccine was recently found to be effective in delaying tumor growth in mice.
“This vaccine is a wonderful example of applying biomaterials to new questions and issues in medicine,” says David Mooney, Ph.D., a professor of bioengineering at Harvard University in the School of Engineering and Applied Sciences, whose lab developed the vaccine. The project was co-led by Jaeyun Kim, Ph.D. and Aileen Li, a doctoral student in the Mooney lab. Their findings were published in the December 8, 2014 issue of Nature Biotechnology.
Cancer cells are generally ignored by the immune system. This is because—for the most part—they more closely resemble cells that belong in the body than pathogens, such as bacterial cells or viruses. The goal of cancer vaccines is to provoke the immune system to recognize cancer cells as foreign and attack them.
One way to do this is by manipulating dendritic cells, the coordinators of immune system behavior. Dendritic cells constantly patrol the body, sampling bits of protein found on the surface of cells or viruses called antigens. When a dendritic cell comes in contact with an antigen that it deems foreign, it carries it to the lymph nodes, where it instructs the rest of the immune system to attack anything in the body displaying that antigen.
Though similar to healthy cells, cancer cells often display unique antigens on their surface, which can be exploited to develop cancer immunotherapies. For example, in dendritic cell therapy, white blood cells are removed from a patient’s blood, stimulated in the lab to turn into dendritic cells, and then incubated with an antigen that is specific to a patient’s tumor, along with other compounds to activate and mature the dendritic cells. These “programmed” cells are then injected back into the bloodstream with the hopes that they will travel to the lymph nodes and present the tumor antigen to the rest of the immune system cells.
Biomaterials boost immunity
While this approach has had some clinical success, in most cases, the immune response resulting from dendritic cell vaccines is short-lived and not robust enough to keep tumors at bay over the long run. In addition, cell therapies such as this, which require removing cells from patients and manipulating them in the lab, are costly and not easily regulated. To overcome these limitations, Mooney’s lab has been experimenting with a newer approach that involves reprogramming immune cells from inside the body using implantable biomaterials.
The idea is to introduce a biodegradable scaffold under the skin that temporarily creates an “infection-mimicking microenvironment”, capable of attracting, housing, and reprogramming millions of dendritic cells over a period of several weeks. In a 2009 paper published in Nature Materials, Mooney demonstrated that this could be achieved by loading a porous scaffold—about the size of a dime—with tumor antigen as well as a combination of biological and chemical components meant to attract and activate dendritic cells. Once implanted, the scaffold’s contents slowly diffused outward, recruiting a steady stream of dendritic cells, which temporarily sought residence inside the scaffold while being simultaneously exposed to tumor antigen and activating factors.
When the scaffold was implanted in mice, it achieved a 90% survival rate in animals that otherwise die from cancer within 25 days.
An injectable scaffold
Now, Mooney and his team have taken this approach a step further, creating an injectable scaffold that can spontaneously assemble once inside the body. This second generation vaccine would prevent patients from having to undergo surgery to implant the scaffold and would also make it easier for clinicians to administer it.
The new 3D vaccine is made up of many microsized, porous silica rods dispersed in liquid. When injected under the skin, the liquid quickly diffuses, leaving the rods behind to form a randomly assembled three-dimensional structure resembling a haystack. The spaces in between the rods are large enough to house dendritic cells and other immune cells, and the rods have nano-sized pores that can be loaded with a combination of antigens and drugs.
When injected into mice that were then given a subsequent injection of lymphoma cells, the 3D vaccine generated a potent immune response and delayed tumor growth. Compared to a bolus injection containing the same drugs and antigens (but no scaffold), the 3D vaccine was more effective at preventing tumor growth, with 90% of mice receiving the 3D vaccine still alive at 30 days compared with only 60% of mice given the bolus injection.
While the 3D injectable scaffold is being tested in mice as a potential cancer vaccine, any combination of different antigens and drugs could be loaded into the scaffold, meaning it could also be used to treat infectious diseases that may be resistant to conventional treatments.
“The ability to so elegantly harness the natural behavior of dendritic cells to elicit a strong immune response is impressive,” says Jessica Tucker, Program Director of Drug and Gene Delivery Systems and Devices at NIBIB. “The possibility of developing this approach as a cancer vaccine, which would not require an invasive and costly surgery to manipulate immune cells outside of the body, is very exciting.”
Mooney says that in addition to continuing to develop the cancer vaccine, he also plans to explore how the injectable scaffold can be used to both treat and prevent infectious diseases. More broadly, Mooney predicts that spontaneously assembling particles will be adopted by many fields in the future.
“I think this is going to be the first of a number of examples where we utilize ideas of self-organization in the body instead of having to create structures outside of the body and place them in,” says Mooney. “I think that will be broadly applicable, not only in instances like this, but also, for example, in tissue engineering and regenerative medicine where scaffolds are used to facilitate the regrowth of tissues in the body. The ability to assemble a scaffold in the body instead of having to surgically implant it would be a significant advance.”
This research was supported in part by the National Institute of Biomedical Imaging and Bioengineering under award #EB015498.
National Institute of Biomedical Imaging and Bioengineering
Mutation detection in human in vitro fertilized embryos using whole-genome sequencing
Pre-implantation genetic diagnosis (PGD) is used in fertility clinics to detect large chromosomal abnormalities or genetic mutations passed on by parents to their in vitro fertilized (IVF) embryos. However, it is not possible to comprehensively scan the embryo’s genome to detect spontaneous mutations. In a study published online in Genome Research, scientists developed a whole-genome sequencing approach using 5- to 10-cell biopsies from human embryos to detect potential disease-causing mutations.
Researchers from Complete Genomics, Reprogenetics, and the NYU Fertility Center sequenced three biopsies from two IVF embryos in attempt to detect de novo mutations, those that arise spontaneously in the egg or sperm and are not inherited from either parent. These types of mutations are thought to account for a large fraction of severe intellectual disability, autism, epileptic encephalopathies, and other congenital disorders.
Since only 5 to 10 cells can be biopsied from a blastocyst embryo, the DNA is amplified before sequencing. This amplification process introduces thousands of errors that appear to be de novo mutations. Until now, it has been difficult to disentangle the sequencing errors from true de novo mutations. Using their previously published method Long Fragment Read (LFR) technology, the researchers assigned DNA fragments to the maternal or paternal genome using DNA barcodes and were able to remove over 100,000 sequencing errors, reducing the error rate approximately 100-fold over previous studies.
“Because each individual carries on average less than 100 de novo mutations, being able to detect and assign parent of origin for these mutations, which are the cause of many diseases, required this extremely low error rate,” said co-corresponding authors Brock Peters and Radoje Drmanac from Complete Genomics. Overall, the researchers detected 82% of all de novo changes in the IVF embryos; this is the first demonstration that a large majority of single base de novo mutations could be detected in a PGD test.
In one embryo, the researchers did not find any de novo mutations in protein-coding regions of the genome. However, in another other embryo from the same couple, the researchers found two coding mutations in the ZNF266 and SLC26A10 genes that may be potentially damaging. The authors point out, however, that it is currently unknown if there would be any health consequences for a child born with these mutations.
“The biggest hurdle now is one of how to analyze the medical impact of detected mutations and make decisions based on those results,” said Peters and Drmanac.
In addition to PGD, this new methodology could be useful for other applications in which cells are limited, such as sequencing circulating tumor cells (CTCs) or circulating fetal cells (CFCs), each of which are present in rare subpopulations in the blood.
Peters BA, Kermani BG, Alferov O, Agarwal MR, McElwain MA, Gulbahce N, Hayden DM Tang YT, Zhang RY, Terle R, Crain B, Prates R, Berkeley A, Munné S, Drmanac R. 2015. Detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing. Genome Res doi: 10.1101/gr.181255.114
DATA RECORDING ENABLES MONITORING, REPORTING & MANAGEMENT OF PROCESS FLOW
Titan Enterprises has released a new data recording version of its Atrato ultrasonic flowmeter software interface. Easy to set-up and use the Atrato flow recorder enables data recording via an external computer. With features that provide monitoring, reporting and management of flow data - the Atrato flow recorder delivers a continuous picture of your process and a reliable alternative to restrictive and costly manual metering. The new software interface will be supplied with all new orders and can also be used with any Atrato flowmeter manufactured after June 2013. The market leading Atrato ultrasonic flowmeter is a true inline non-invasive flow meter without the contorted flow path and disadvantages of alternative designs. It can handle flows from laminar to turbulent and is therefore largely immune from viscosity. It also offers excellent turndown, linearity and repeatability. Available in 60°C and 110°C temperature versions and a 30 bar higher pressure model - Atrato flowmeters use patented 'time-of-flight' ultrasonic technology that enables it to operate over very wide flow ranges (200:1) with excellent accuracy (better than ±1.0% of reading). Using the new Atrato flow recorder - users can select from a wide variety of functions and time periods over which to store their results. Flow data sets are saved as .csv files which can then be imported directly to a wide range of programmes for later manipulation and analysis. Data recording can be set up to be every number of samples or actual readings averaged over a time period. Examples of data recorded include actual flow rate, filtered flow rate, total, output transistors, analogue outputs and ultrasonic signal strength.
POLYSACCHARIDE DERIVATIVES EXTEND THE YMC CHIRAL PORTFOLIO!
In the past few years only a limited number of “good” chiral chromatographic materials have been established. Restrictions due to selectivity and the use of specific solvents (stability) had to be tolerated. As a result, these “good” chiral materials were expensive and often limited in their availability for preparative uses. With the arrival of the new CHIRAL ART polysaccharide product range, YMC has successfully delivered truly economic alternatives: for analytical as well as preparative applications! CHIRAL ART polysaccharides are available in pre packed columns with 3, 5, 10 and 20 μm particle sizes. Method development can be carried out on an analytical material and then seamlessly converted to preparative scale: 20 μm and 10 μm materials in bulk available – in multi-kilogram amounts.
HOTPLATE STIRRER FOR SYNTHETIC CHEMISTRY
Asynt hotplate stirrers are designed to offer synthetic chemistry laboratories a combination of affordability, top build quality and high performance without compromising on safety. Manufactured in an ISO9001-2008 production facility, each Asynt hotplate stirrer incorporates two independent control circuits. The additional and independent safety circuit is for limiting the maximum heating plate temperature, this can be adjusted between 50 and 360 ºC but cannot be changed accidentally. This ensures that the flashpoint of your reaction solvent is not exceeded making it ideal for teaching laboratories. A hermetically sealed design protects the hotplate stirrer motor assembly from spillages ensuring long-term reliability and enhanced operator safety. For labs looking to regularly undertake unattended overnight reactions, Asynt hotplate stirrer packages are supplied with an additional third temperature controller which improves reproducibility and accuracy to 0.5°C and the ultimate in operational safety. Asynt hotplate stirrers also feature a very powerful magnetic drive with ramp start function, especially useful when stirring more viscous samples or for parallel synthesis of multiple tubes or flasks with devices such as the DrySyn MULTI. A highly polished aluminium hotplate provides optimum heat transfer thereby ensuring top performance. Asynt hotplate stirrers can be supplied as part of a discounted package including hotplate stirrer, temperature sensor, electronic contact thermometer, holding rod, support rod and the boss head clamp so that you're all set to start heating at controlled temperatures.
DIRTY WATER FLOW METER IMPROVES RELIABILITY OF GLASS BOTTLE MAKING PLANT
Titan Enterprises reports on development of a ‘dirty water’ ultrasonic flowmeter for Graphoidal Developments Ltd.
Graphoidal Developments has established itself at the forefront of designing and manufacturing the most advanced lubrication and coating systems for the glass container and tableware industries. Their expertise is in precise pumping, control of mixing, dosing and spraying of the lubricants and coatings which form a vital part of the glass production process, both in hot end and cold end areas. Graphoidal Developments first started using Titans turbine flowmeters over twenty years ago. They install flowmeters in their water lines to monitor the application of the coolant to the shears which are used to cut semi-molten glass in bottle making machines. The accurate application of a lubricant and coolant is critical to the reliability of the whole machine. Initial installations of Graphoidal machines in Europe, fitted with Titan flowmeters, proved very reliable. However as the success of the Graphoidal machines spread worldwide a flow monitoring problem became apparent. Older glass bottle making plants often had steel piping which rusted. The deposition of rust in the water coolant lines not only abraded the machines bearings but also rendered the turbine flowmeters inaccurate. Graphoidal recognised in some locations a regular supply of clean potable water was not possible and excessive filtering (to remove rust) with the corresponding pressure drop and reduced service intervals were not options. As a result - Graphoidal approached Titan Enterprises to develop an alternative flowmeter that would be immune to the ‘dirty water’ problem, could operate over a wide dynamic flow range, had identical electronic outputs and would fit into the same space as the existing turbine flowmeter. It became apparent that Titan’s proprietary Atrato ultrasonic flowmeter technology offered a solution but required modification to fit in the desired space and reduction of the sophisticated electronics to help meet target unit prices. Titan Enterprises started with a blank sheet of paper and used a bit of lateral thinking to solve the problem. The pipe connections on Graphoidal machines were fixed so Titan chose to turn the Atrato flowmeter sensing element to be 90° to the fluid path with a manifold to make the connections. Unfortunately this made the meter just too big for the available cabinet space. Titan then experimented with bending the flow passage around 180° whilst still carrying the ultrasound. Using unique algorithms this technique proved to be successful so the sensors could be placed on the manifold and both the flow and the ultrasonic signals being bent around a 28mm diameter 180° arc. In addition the flowmeter electronics were re-designed to match the customer’s specification and any extraneous functions not required by Graphoidal machines eliminated. The closure for the housing was made into a robust plastic cover to keep the costs down. While the resulting product is more expensive than the turbine flowmeter it replaced its advantages far outweigh the drawbacks. Each meter has an identical ‘K’ factor so no individual calibration of a Graphoidal machines PLC is required. A single ultrasonic flowmeter is able to cover multiple flow ranges enabling reduced inventory to be held by Graphoidal. As the Atrato ultrasonic flowmeter has no moving parts, there are no parts to wear out due to rust abrasion. The flowmeter has proven itself highly reliable, even in some of the former troublesome plants, so far fewer call outs for faulty measurement systems due to inferior water supplies have been required. Consequently Graphoidal’s customers are happy and the company’s reputation has further improved within the industry.
DIRECT CONCENTRATION OF LARGE SAMPLE VOLUMES INTO VIALS
SampleGenie 4 is the latest version of Genevac’s unique technology for direct concentration of large sample volumes into vials, designed for use in the Rocket Synergy Evaporator. SampleGenie technology enables large sample volumes to be dried directly into vials, eliminating a number of time-consuming sample handling steps and the attendant risk of errors. The latest generation SampleGenie further enhances the exceptional capabilities of the original design. Accommodating sample volumes of up to 250ml, and featuring a new vial adapter insert to suit a range of vials from 12mm to 28mm diameter and up to 70mm tall. SampleGenie 4 has been precision engineered to reduce the risk of vial breakage. Traditionally protocols for concentration of chromatographic fractions has involved drying multiple fractions in an evaporator, re-suspending pooled fractions into a single vial and then re-drying before storage and analysis. Even with modern centrifugal evaporators such processes typically take 2-3 days to complete. The development of SampleGenie™ technology has revolutionised this process enabling samples in Genevac Rocket Synergy, HT and EZ-2 series evaporators to be dried or concentrated, directly into a single vial eliminating the need for reformatting of samples after drying. This, and the automation offered by Genevac evaporators simplifies the protocol to a single overnight drying step before storage or analysis. Not only does SampleGenie remove time consuming manual steps - it lowers labour costs and improves data reliability. SampleGenie technology, in conjunction with Genevac evaporators, is finding widespread use in applications including environmental analysis, metabolism and toxicology studies, food and beverage research as well as post purification protocols in chemical / life science research.
CONTROLLED EVAPORATION PRODUCES REPRODUCIBLY LARGE CRYSTALS
Genevac reports its non-destructive evaporation technology - eXalt has been used by several research groups to produce larger crystals than was previously possible using traditional methods. Crystallisation is a critical step in the development of many compounds, it can form part of a purification or separation protocol and can influence yield, purity and particle size. Chemists achieve crystallisation by many varied methods. Variation in temperature, solvent, head pressure, seeding method and evaporation rate can all have an effect on the crystallisation process, influencing the form, shape and size of crystals formed. Until the advent of eXalt technology, traditional crystallisation methods have offered little control and often no reproducibility over these parameters. Genevac's patented eXalt technology enables a wide range of solvents and multiple actives to be evaporated all at the same slow rate, and under the same conditions, giving the user unprecedented control of the crystallisation process. This is achieved using a special holder which can be configured to slow the evaporation rate of each solvent, i.e. the more volatile solvents are impeded more, and some solvents such as water, need no restriction. The holder is then placed in the controlled conditions of a Genevac HT Series Evaporator which cycles the pressure over the samples to create a draw, achieving controlled, even evaporation. eXalt holders can accept up to 24 different samples, and 4 8 or 12 holders can be placed in the evaporator, depending on size. Areas of application that have particularly benefited from eXalt technology include screening for crystal forms of new compounds, re-crystallisation of existing compounds into new forms, confirmation of stable isomeric forms, production of large seed crystals, co-crystal studies and crystallisation of compounds where only amorphous forms had previously been identified.
NON DUCTED FUME CUPBOARDS
Asynt announces a new range of high quality, non-ducted fume cupboards designed to sit on a standard laboratory bench.
Available in standard widths from 550mm to 900mm wide, all Asynt fume cupboards are fully compliant with COSHH regulations and international standards including BS7989:2001 for filtration fume / particulate cupboards. During manufacture, every aspect of the cabinet, from the electrics to the metalwork, is meticulously checked and monitored to ensure high reliability, optimal operation and safety is achieved. All Asynt fume cupboards employ extra-large capacity activated carbon filters for removal of fumes and/or HEPA filters for particulate removal. The filters are up to 30% bigger than that of rival systems and also significantly deeper making fume removal more efficient, effective and therefore providing improved safety. Fume cupboards may be supplied with an optional dual filtration capability (carbon/carbon, carbon/HEPA or HEPA/HEPA) making them suitable for highly effective use with volatile solvents, toxic chemical work as well as safely containing dust and particulate hazards.
The new range of Asynt non-ducted fume cupboards come with an industry-leading 5 year warranty. This means Asynt will warrant units to be free from defects in materials or workmanship for a period of 5 years from the date of delivery.
KINESIS EXTENDS PARTNERSHIP WITH TRAJAN FOR SGE DISTRIBUTION IN THE US
Kinesis and Trajan Scientific and Medical (Trajan) are pleased to announce Kinesis as an approved distribution partner for the SGE Analytical Science (SGE) range of Chromatography Consumables in the US. SGE is a Trajan brand, established in 1960 and integrated into Trajan in 2013. The SGE brand is well known for its diamond syringe quality and is the global market leader in niche areas such as autosampler syringes and GC inlet liners. Trajan’s focus is on developing and commercializing technologies that enable analytical systems to be more selective, sensitive and specific for biological, environmental or food related measurements especially those that can lead to portability, miniaturization and affordability. Chief Executive Officer of Trajan, Stephen Tomisich said: “Thinking on both a global and local scale is critical for us. We identify key partners around the world to help us deliver a great local customer experience. The individuals that ultimately use our products are front of mind”.
www.kinesis-usa.com - www.sge.com
BIOCON FOUNDATION RECOGNIZED FOR OUTSTANDING CONTRIBUTION TO PUBLIC HEALTH BY WHO-INDIA
Biocon Ltd., Asia's premier biotechnology company, has announced that Biocon Foundation, its CSR arm, is the proud recipient of 'WHO-India Public Health Champion Award 2015' for its initiatives in the area of public health. Biocon Foundation has been recognized for its integrated healthcare initiatives through which it is constantly engaged in improving the quality of life of several thousand communities in India. The 'Public Health Champion Award 2015' is a new initiative by World Health Organization-India. The awards were presented at a national consultation held to commemorate the World Health Day 2015. Ms. Rani Desai, Head of Biocon Foundation, received the award from Dr. Nata Menabde, WHO representative to India, at a function held in New Delhi. Expressing her delight at receiving the award, Ms Rani Desai, Head, Biocon Foundation said: "The Foundation has been recognized for its innovative healthcare models of preventive and primary health services through which we are engaged in creating a sustainable health ecosystem. Through our primary health clinics we aim to enable access to affordable healthcare to rural and urban marginalized communities".
NOVASEP AND CELLADON EXECUTE MYDICAR API SUPPLY AGREEMENT
Novasep and Celladon Corporation have announced that they have signed a Development, Manufacturing and Supply Agreement pursuant to which, if supported by upcoming MYDICAR clinical data, Novasep would manufacture MYDICAR drug substance through 2018 with extension options through 2020. The contract follows an earlier letter agreement concerning the initial process transfer of MYDICAR and pre-validation studies, which was signed in December 2014. The new agreement continues the work necessary for Novasep to achieve GMP production of MYDICAR drug substance. MYDICAR is an innovative, genetically-targeted enzyme replacement therapy based on AAV1/SERCA2a that is being developed for advanced heart failure and has been granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA). MYDICAR is currently being tested in human clinical trials, including a Phase IIb study in the USA and Europe referred to as CUPID2, the top-line results of which are expected to be announced in late April 2015.
APTAR PHARMA RECOGNIZES WORLD PARKINSON’S DAY
Aptar Pharma presents a new scientific white paper, following its recent roundtable held in Paris, France. The goal of this roundtable was to explore and exchange views on the challenges, approaches and opportunities that exist with regard to effectively crossing the blood-brain barrier (BBB) and successfully treating a host of central nervous system (CNS) diseases. The CNS, which comprises the brain, spinal cord and a complex system of neurons, integrates and responds to sensory information, playing a key role by coordinating body function. Diseases such Parkinson’s and Alzheimer’s are CNS disorders that affect a growing population. Although many molecules can be used to treat brain and more generally, CNS diseases, today, only 1% of these molecules can cross the BBB, a “firewall” that allows the passage of oxygen and nutrients but blocks the entrance of what it considers harmful or toxic molecules into the brain. The challenge therefore lies in identifying potential routes for drug delivery, hence the title of the roundtable: “Crossing the Blood-Brain Barrier, Which Route to Take?”
EUROGENTEC COMPLETES MANUFACTURE OF 150 G OF GMP PLASMID DNA
Eurogentec, a custom service and contract manufacturing organization (CMO), has announced that its GMP Drug Substance manufacturing facility has completed the production of 150 grams of plasmid DNA (pDNA). The GMP plasmid was manufactured and released as a single GMP batch and is the largest batch of pDNA ever manufactured. The plasmid DNA was manufactured in a facility that has been inspected by the US FDA and the material is intended for use in human clinical trials to take place in the USA and Europe. Ingrid Dheur, Business Unit Director at Eurogentec, stated: "This successful production confirms that Eurogentec’s platform GMP plasmid production process is scalable to at least 150 g per batch; we are now evaluating steps required to reach the kilogram scale to prepare for our current clients projected needs".
METTLER TOLEDO TDL ANALYZERS RECEIVE AWARD FROM FROST & SULLIVAN FOR COMPETITIVE STRATEGY INNOVATION & LEADERSHIP
Mettler-Toledo's GPro 500 TDL series has received the 2014 Global Frost & Sullivan Award for Competitive Strategy Innovation & Leadership. The series offers both a probe and a wafer cell for the measurement of gases in different types of processes. Based on its recent analysis of the process tunable diode laser (TDL) analysers market, Frost & Sullivan recognizes Mettler-Toledo AG with the 2014 Global Frost & Sullivan Award for Competitive Strategy Innovation & Leadership. Mettler-Toledo's TDL series, the GPro 500, has an original design that is adaptable to almost any kind of process. The series comprises four separate products for the measurement of oxygen, carbon monoxide, carbon dioxide, and moisture. Mettler-Toledo's GPro 500 TDL series can be used for both in-situ and extractive measurement. In-situ measurement is increasingly preferred by customers, as direct measurement in the process is fast and reliable. Others prefer extractive systems where a sample of the gas is literally extracted from the gas stream before measurement. The GPro 500 combines the laser source and Analyzer in a single unit. The laser beam from the source passes down a probe and is reflected by a three-sided mirror back up the probe to the Analyzer. This design makes alignment unnecessary. The GPro 500 TDL series is available with a range of adaptions that fit directly to the analyser’s head. These adaptions are the reason for the GPro 500's flexibility in application.
CRO TO EXPAND GMP CAPABILITY
UK-based Onyx Scientific is to invest in growing its GMP space following an increase in demand for its small scale API manufacturing services. The move will see the installation of a new Class 100,000 suite at its facility in North East England aimed at satisfying an upsurge in Phase I/II GMP campaigns from clients in Europe and the USA. Onyx Scientific specialises in pre-clinical/clinical development projects and expansion plans were given the go ahead at the contract research organisation (CRO) following another successful audit by the MHRA in February. Celebrating its 15th birthday this year, the CRO provides clients with the production of API up to 50l-100l under current GMP regulations, which dovetails its earlier stage custom synthesis, lead optimisation, solid state and analytical services. Denise Bowser, commercial director at Onyx Scientific, said: “This latest investment will bring the total capacity at our UK site up to four dedicated GMP suites, which represents a steady but significant growth in this area over the past few years. “We have worked with hundreds of clients at the small scale non-GMP stage and have been able to provide rapid scale up to GMP for many of them with the same technical team, all under one roof”. “So by having an additional GMP suite at our disposal, it gives us even greater flexibility to assist our clients that are under increasing timeline pressure to deliver against their development programs”.