|By PR Newswire||
|January 17, 2014 07:00 AM EST||
ST. LOUIS, Jan. 17, 2014 /PRNewswire/ -- Sigma-Aldrich Corporation (NASDAQ: SIAL) today announced that Sigma Life Science, its innovative biological products and services business, will be launching the genetically-modified HepaRG human liver cell line, licensed from Biopredic, for hepatotoxicity and drug metabolism assays. Currently undergoing beta-testing by multiple contract research and pharmaceutical organizations, the assays will be publicly available later in Q1 2014 in a plated, live-cell format to support translational research in industry and academia. Through this license agreement with BioPredic International, Sigma-Aldrich will also offer high-quality wild-type HepaRG liver cells and supporting media.
In drug discovery and development, unforeseen toxicity issues, particularly in the liver, remain a major cause of late-stage drug failures that account for billions of dollars of lost pharmaceutical R&D investments. This has recently prompted regulators and pharmaceutical companies to issue guidance and develop robust studies to predict liver toxicity. However, current assays using animals or in vitro techniques—such as utilizing small molecule inhibitors, RNAi, or less than desirable cell lines—introduce biological ambiguity, off-target effects or limit the extent of acquirable data.
To generate novel, precision assays for early prediction of hepatic liabilities, Sigma-Aldrich will apply its exclusive CompoZr® Zinc Finger Nuclease (ZFN) gene editing technology on the HepaRG human liver cells. Sigma-Aldrich plans to knock-out genes for critical xenobiotic sensors—such as PXR and CAR—and drug transporters—including BSEP, OATP1B1, and OATP1B3—that regulatory agencies have highlighted for possible analysis. The gene knock-out approach, only recently possible in human cells due to the advent of robust gene-editing tools such as CompoZr ZFNs, eliminates the ambiguities about a drug's interactions that would be introduced by conventional tools, such as small molecules or RNAi. Sigma-Aldrich will also knock-in fluorescence reporter tags to endogenous toxicity biomarkers, such as ALT and Cytochrome P450, to generate inexpensive, high-throughput live cell imaging or reporter-based assays that can reveal toxic drug effects and drug–drug interactions.
"Such precision assays currently do not exist. These gene-edited HepaRG cell-based assays represent a major improvement in the quality of data compared to the predominant way of studying liver drug metabolism and toxicity, which is through primary human hepatocytes recovered from donated cadavers. These primary cells suffer from sporadic availability, loss of in vivo functions, variable donor health, and genetic polymorphisms that can confound reproducible analyses," explained Paul Brooks, Ph.D, Global Market Manager at Sigma-Aldrich.
The HepaRG immortalized cell lines from BioPredic International are unique in that they mirror the endogenous human hepatocyte functionality and metabolism(1,2,3) providing a dependable supply of long-lifespan, isogenic cells that eliminate confounding sources of variation. Other immortalized liver cell lines exist, including Fa2N-4 and HepG2, but all of these cell lines lack important biological features, such as expression of the Cyp3A4 enzyme that metabolizes more than 50% of currently approved drugs.
The beta testing program for the genetically-modified HepaRG cell lines is currently open to CRO, pharmaceutical, and academic partners.
Sigma-Aldrich currently offers several gene-edited human cell lines for ADME/Tox assays, including Caco-2 human liver cell lines with efflux transporter gene knock-outs for clear analysis of potential drug–drug interactions.
"The broad vision for Sigma-Aldrich's ADME/Tox R&D is to exploit gene-editing in human cell lines to provide novel, isogenic assays that resolve fundamental shortfalls in current ADME/Tox methodologies. By doing so, we can resolve a major hurdle in translational research,leading to safer drugs and more sustainable drug development programs," said Sean Muthian, Ph.D., Director of Strategic Marketing at Sigma-Aldrich.
For more information, visit sigma.com/admetox.
(1) Kanebratt et al. (2008) Drug Metab Dispos 36,137-145
(2) Hart et al. (2010) Drug Metab Dispos 38, 988-994
(3) McGill et al. (2011) Hepatology 53, 974-982
Cautionary Statement: The foregoing release contains forward-looking statements that can be identified by terminology such as "will be publicly available," "early prediction", "precision" or similar expressions, or by expressed or implied discussions regarding potential future revenues from products derived there from. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that this or any other joint venture will assist the Company to achieve any particular levels of revenue in the future. In particular, management's expectations regarding this joint venture could be affected by, among other things, the Company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Company's assets and liabilities as recorded in its consolidated balance sheet, and other risks and factors referred to in Sigma-Aldrich's current Form 10-K on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Sigma-Aldrich is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Sigma-Aldrich: Sigma-Aldrich, a leading Life Science and High Technology company focused on enhancing human health and safety, manufactures and distributes more than 200,000 chemicals, biochemicals and other essential products to more than 1.4 million customers globally in research and applied labs as well as in industrial and commercial markets. With three distinct business units – Research, Applied and SAFC Commercial – Sigma-Aldrich is committed to enabling science to improve the quality of life. The Company operates in 38 countries, has more than 9,000 employees worldwide and had sales of $2.6 billion in 2012. For more information about Sigma-Aldrich, please visit its website at www.sigma-aldrich.com.
Sigma-Aldrich and Sigma are trademarks of Sigma-Aldrich Co. LLC registered in the US and other countries. CompoZr is a trademark of Sigma-Aldrich Co. LLC. HepaRG is a trademark of BioPredic International.
SOURCE Sigma-Aldrich Corporation
There is an ever-growing explosion of new devices that are connected to the Internet using “cloud” solutions. This rapid growth is creating a massive new demand for efficient access to data. And it’s not just about connecting to that data anymore. This new demand is bringing new issues and challenges and it is important for companies to scale for the coming growth. And with that scaling comes the need for greater security, gathering and data analysis, storage, connectivity and, of course, the...
May. 4, 2016 03:30 AM EDT Reads: 1,131
The IoTs will challenge the status quo of how IT and development organizations operate. Or will it? Certainly the fog layer of IoT requires special insights about data ontology, security and transactional integrity. But the developmental challenges are the same: People, Process and Platform. In his session at @ThingsExpo, Craig Sproule, CEO of Metavine, will demonstrate how to move beyond today's coding paradigm and share the must-have mindsets for removing complexity from the development proc...
May. 4, 2016 03:00 AM EDT Reads: 775
Redis is not only the fastest database, but it has become the most popular among the new wave of applications running in containers. Redis speeds up just about every data interaction between your users or operational systems. In his session at 18th Cloud Expo, Dave Nielsen, Developer Relations at Redis Labs, will shares the functions and data structures used to solve everyday use cases that are driving Redis' popularity.
May. 4, 2016 12:45 AM EDT Reads: 1,180
Much of the value of DevOps comes from a (renewed) focus on measurement, sharing, and continuous feedback loops. In increasingly complex DevOps workflows and environments, and especially in larger, regulated, or more crystallized organizations, these core concepts become even more critical. In his session at @DevOpsSummit at 18th Cloud Expo, Andi Mann, Chief Technology Advocate at Splunk, will show how, by focusing on 'metrics that matter,' you can provide objective, transparent, and meaningfu...
May. 3, 2016 11:45 PM EDT Reads: 1,010
Many private cloud projects were built to deliver self-service access to development and test resources. While those clouds delivered faster access to resources, they lacked visibility, control and security needed for production deployments. In their session at 18th Cloud Expo, Steve Anderson, Product Manager at BMC Software, and Rick Lefort, Principal Technical Marketing Consultant at BMC Software, will discuss how a cloud designed for production operations not only helps accelerate developer...
May. 3, 2016 11:30 PM EDT Reads: 1,237
Manufacturers are embracing the Industrial Internet the same way consumers are leveraging Fitbits – to improve overall health and wellness. Both can provide consistent measurement, visibility, and suggest performance improvements customized to help reach goals. Fitbit users can view real-time data and make adjustments to increase their activity. In his session at @ThingsExpo, Mark Bernardo Professional Services Leader, Americas, at GE Digital, will discuss how leveraging the Industrial Interne...
May. 3, 2016 11:00 PM EDT Reads: 1,293
Artificial Intelligence has the potential to massively disrupt IoT. In his session at 18th Cloud Expo, AJ Abdallat, CEO of Beyond AI, will discuss what the five main drivers are in Artificial Intelligence that could shape the future of the Internet of Things. AJ Abdallat is CEO of Beyond AI. He has over 20 years of management experience in the fields of artificial intelligence, sensors, instruments, devices and software for telecommunications, life sciences, environmental monitoring, process...
May. 3, 2016 11:00 PM EDT Reads: 1,210
The IETF draft standard for M2M certificates is a security solution specifically designed for the demanding needs of IoT/M2M applications. In his session at @ThingsExpo, Brian Romansky, VP of Strategic Technology at TrustPoint Innovation, will explain how M2M certificates can efficiently enable confidentiality, integrity, and authenticity on highly constrained devices.
May. 3, 2016 10:00 PM EDT Reads: 1,212
Increasing IoT connectivity is forcing enterprises to find elegant solutions to organize and visualize all incoming data from these connected devices with re-configurable dashboard widgets to effectively allow rapid decision-making for everything from immediate actions in tactical situations to strategic analysis and reporting. In his session at 18th Cloud Expo, Shikhir Singh, Senior Developer Relations Manager at Sencha, will discuss how to create HTML5 dashboards that interact with IoT devic...
May. 3, 2016 10:00 PM EDT Reads: 1,324
We're entering the post-smartphone era, where wearable gadgets from watches and fitness bands to glasses and health aids will power the next technological revolution. With mass adoption of wearable devices comes a new data ecosystem that must be protected. Wearables open new pathways that facilitate the tracking, sharing and storing of consumers’ personal health, location and daily activity data. Consumers have some idea of the data these devices capture, but most don’t realize how revealing and...
May. 3, 2016 09:45 PM EDT Reads: 346
SYS-CON Events announced today that Ericsson has been named “Gold Sponsor” of SYS-CON's @ThingsExpo, which will take place on June 7-9, 2016, at the Javits Center in New York, New York. Ericsson is a world leader in the rapidly changing environment of communications technology – providing equipment, software and services to enable transformation through mobility. Some 40 percent of global mobile traffic runs through networks we have supplied. More than 1 billion subscribers around the world re...
May. 3, 2016 08:45 PM EDT Reads: 1,283
In the world of DevOps there are ‘known good practices’ – aka ‘patterns’ – and ‘known bad practices’ – aka ‘anti-patterns.' Many of these patterns and anti-patterns have been developed from real world experience, especially by the early adopters of DevOps theory; but many are more feasible in theory than in practice, especially for more recent entrants to the DevOps scene. In this power panel at @DevOpsSummit at 18th Cloud Expo, moderated by DevOps Conference Chair Andi Mann, panelists will dis...
May. 3, 2016 08:45 PM EDT Reads: 972
We’ve worked with dozens of early adopters across numerous industries and will debunk common misperceptions, which starts with understanding that many of the connected products we’ll use over the next 5 years are already products, they’re just not yet connected. With an IoT product, time-in-market provides much more essential feedback than ever before. Innovation comes from what you do with the data that the connected product provides in order to enhance the customer experience and optimize busi...
May. 3, 2016 08:30 PM EDT Reads: 1,210
The increasing popularity of the Internet of Things necessitates that our physical and cognitive relationship with wearable technology will change rapidly in the near future. This advent means logging has become a thing of the past. Before, it was on us to track our own data, but now that data is automatically available. What does this mean for mHealth and the "connected" body? In her session at @ThingsExpo, Lisa Calkins, CEO and co-founder of Amadeus Consulting, will discuss the impact of wea...
May. 3, 2016 08:00 PM EDT Reads: 1,057