Welcome!

News Feed Item

Sigma® Life Science Launching Genetically-Modified HepaRG™ Human Liver Cells Licensed from Biopredic for Cell-based ADME/Tox Assays

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

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
Between 2005 and 2020, data volumes will grow by a factor of 300 – enough data to stack CDs from the earth to the moon 162 times. This has come to be known as the ‘big data’ phenomenon. Unfortunately, traditional approaches to handling, storing and analyzing data aren’t adequate at this scale: they’re too costly, slow and physically cumbersome to keep up. Fortunately, in response a new breed of technology has emerged that is cheaper, faster and more scalable. Yet, in meeting these new needs they...
"We're a cybersecurity firm that specializes in engineering security solutions both at the software and hardware level. Security cannot be an after-the-fact afterthought, which is what it's become," stated Richard Blech, Chief Executive Officer at Secure Channels, in this SYS-CON.tv interview at @ThingsExpo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
When it comes to cloud computing, the ability to turn massive amounts of compute cores on and off on demand sounds attractive to IT staff, who need to manage peaks and valleys in user activity. With cloud bursting, the majority of the data can stay on premises while tapping into compute from public cloud providers, reducing risk and minimizing need to move large files. In his session at 18th Cloud Expo, Scott Jeschonek, Director of Product Management at Avere Systems, discussed the IT and busin...
According to Forrester Research, every business will become either a digital predator or digital prey by 2020. To avoid demise, organizations must rapidly create new sources of value in their end-to-end customer experiences. True digital predators also must break down information and process silos and extend digital transformation initiatives to empower employees with the digital resources needed to win, serve, and retain customers.
The IoT is changing the way enterprises conduct business. In his session at @ThingsExpo, Eric Hoffman, Vice President at EastBanc Technologies, discussed how businesses can gain an edge over competitors by empowering consumers to take control through IoT. He cited examples such as a Washington, D.C.-based sports club that leveraged IoT and the cloud to develop a comprehensive booking system. He also highlighted how IoT can revitalize and restore outdated business models, making them profitable ...
In his general session at 19th Cloud Expo, Manish Dixit, VP of Product and Engineering at Dice, discussed how Dice leverages data insights and tools to help both tech professionals and recruiters better understand how skills relate to each other and which skills are in high demand using interactive visualizations and salary indicator tools to maximize earning potential. Manish Dixit is VP of Product and Engineering at Dice. As the leader of the Product, Engineering and Data Sciences team at D...
SaaS companies can greatly expand revenue potential by pushing beyond their own borders. The challenge is how to do this without degrading service quality. In his session at 18th Cloud Expo, Adam Rogers, Managing Director at Anexia, discussed how IaaS providers with a global presence and both virtual and dedicated infrastructure can help companies expand their service footprint with low “go-to-market” costs.
Get deep visibility into the performance of your databases and expert advice for performance optimization and tuning. You can't get application performance without database performance. Give everyone on the team a comprehensive view of how every aspect of the system affects performance across SQL database operations, host server and OS, virtualization resources and storage I/O. Quickly find bottlenecks and troubleshoot complex problems.
"Once customers get a year into their IoT deployments, they start to realize that they may have been shortsighted in the ways they built out their deployment and the key thing I see a lot of people looking at is - how can I take equipment data, pull it back in an IoT solution and show it in a dashboard," stated Dave McCarthy, Director of Products at Bsquare Corporation, in this SYS-CON.tv interview at @ThingsExpo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
"We are the public cloud providers. We are currently providing 50% of the resources they need for doing e-commerce business in China and we are hosting about 60% of mobile gaming in China," explained Yi Zheng, CPO and VP of Engineering at CDS Global Cloud, in this SYS-CON.tv interview at 19th Cloud Expo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
Predictive analytics tools monitor, report, and troubleshoot in order to make proactive decisions about the health, performance, and utilization of storage. Most enterprises combine cloud and on-premise storage, resulting in blended environments of physical, virtual, cloud, and other platforms, which justifies more sophisticated storage analytics. In his session at 18th Cloud Expo, Peter McCallum, Vice President of Datacenter Solutions at FalconStor, discussed using predictive analytics to mon...
The Internet of Things 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 and how we integrate our thinking to solve complicated problems. In his session at 19th Cloud Expo, Craig Sproule, CEO of Metavine, demonstrated how to move beyond today's coding paradigm and sh...
Today we can collect lots and lots of performance data. We build beautiful dashboards and even have fancy query languages to access and transform the data. Still performance data is a secret language only a couple of people understand. The more business becomes digital the more stakeholders are interested in this data including how it relates to business. Some of these people have never used a monitoring tool before. They have a question on their mind like “How is my application doing” but no id...
@GonzalezCarmen has been ranked the Number One Influencer and @ThingsExpo has been named the Number One Brand in the “M2M 2016: Top 100 Influencers and Brands” by Onalytica. Onalytica analyzed tweets over the last 6 months mentioning the keywords M2M OR “Machine to Machine.” They then identified the top 100 most influential brands and individuals leading the discussion on Twitter.
DevOps is being widely accepted (if not fully adopted) as essential in enterprise IT. But as Enterprise DevOps gains maturity, expands scope, and increases velocity, the need for data-driven decisions across teams becomes more acute. DevOps teams in any modern business must wrangle the ‘digital exhaust’ from the delivery toolchain, "pervasive" and "cognitive" computing, APIs and services, mobile devices and applications, the Internet of Things, and now even blockchain. In this power panel at @...