French biotech Cisbio this week said the French government has awarded it $1.9 million to fund the Intracellular Molecular Imaging project, a private-public research effort Cisbio is leading to develop new cell-based assays for quantifying biomolecular interactions in drug discovery.
Cisbio said the main goal of the IMI will be to develop technology that is compatible with high-throughput screening and that will enable researchers to quantify biomolecular interactions in living cells, specifically targeting G-protein coupled receptors.
Cisbio, a Schering AG subsidiary, does not expect to reap direct monetary or commercialization benefits from the project, but the money could indirectly support its R&D efforts and help it identify ways to bolster its flagship homogenous time-resolved fluorescence (HTRF) assay product portfolio. This would allow the company to better compete with large rivals such as PerkinElmer, Invitrogen, and DiscoverX, all of whom also offer homogenous mix-and-read cell-based assays for drug screening.
The project is also expected to increase Cisbio’s future involvement in academic research and may enable it to cultivate additional relationships with drug-screening instrument vendors.
The IMI was one of 70 of approximately 400 project applications France’s recently established National Research Agency selected to fund in the area of biology and healthcare technological innovation.
Known by its French abbreviation ANR, the agency was created by the French government in 2005 to fund promising research projects in France and, in particular, to encourage partnerships between private and public entities. The agency’s website is not complete and does not yet offer a complete list of award recipients.
Cisbio’s primary partner in the IMI project is the Institut de Génomique Fonctionnelle, located in Montpelier, but the company will also be working with several other undisclosed biotechnology companies, it said in a statement this week.
One of IGF’s research specialties is G-protein coupled receptors, one of the most important target families in drug discovery. Cisbio said IMI’s main goal will be to develop a technology that is compatible with high-throughput screening, and that will enable researchers to quantify biomolecular interactions in living cells, specifically targeting GPCRs.
Specifically, Cisbio and the IGF will develop new techniques for tagging specific intracellular proteins of interest with long-lived fluorescent tracers, and for studying protein interactions in cells using the company’s proprietary HTRF technology, which is based on the concept of time-resolved fluorescence resonance energy transfer (TR-FRET).
“We are aiming to combine the features of the HTRF technology – mainly throughput and ease-of-use – into cellular assays, and to implement this in living cells, without any permeabilization or that sort of thing,” Francois Degorce, Cisbio’s marketing manager for the HTRF product line, told CBA News this week.
Although money from the grant does not go directly into Cisbio’s pocket, it will help fund human resources and equipment needed to support the joint research project, Degorce said.
In addition, although Cisbio does not yet have commercialization rights to specific technologies developed in the collaboration, Degorce said that the research contract will confer R&D knowledge that will benefit its existing HTRF product line. “We are sure there will be a secondary impact from this.”
Cisbio’s flagship HTRF technology is a mix-and-read endpoint assay that is performed on fresh cell lysate to measure a broad array of biomolecular events such as GPCR activation, kinase activation, and protein-protein interactions.
The assay is compatible with high-throughput screening because of the simple preparation, excitation, and readout procedure. However, like many high-throughput assays of its kind, it has limitations. Because the cells aren’t alive when the assay is performed, it lacks physiological relevance; and because the cell has been destroyed, it doesn’t allow researchers to assess the sub-cellular location of a biological event.
“We’ve been through this before, and it was a major hurdle being in a marketplace where the equipment was not ready, was not there, was not compatible, and we don’t particularly want to go through that again.”
High-content cellular imaging can be used to interrogate biomolecular events in living cells, and can often pinpoint their locations, as well. However, high-content screening can’t match the throughput of HTS, and therefore is not useful for primary screening purposes.
According to Degorce, the IMI hopes to develop technologies that will bridge this gap by allowing researchers to interrogate GPCR activation, kinase activation, and protein-protein interactions in living cells, as well as to better understand where they are occurring in the cell without using actual imaging techniques.
“Our idea is to develop a technology platform that is easier to use compared with imaging technologies,” Degorce said. “Basically, one of the drawbacks of current imaging technologies is the capital equipment investment required. This includes specific readers, software, sometimes licenses, and so on and so forth. And those technologies do not always fulfill all the requirements in terms of throughput for HTS.
“And when we say imaging, it might be a simple readout that reflects the localization of the fluorescence,” he added. “The main aim of the project is to make sure the throughput and ease of use is preserved, but the assay works in a cellular environment to mimic physiopathological conditions. This has been a main request of our customers: functional assays in living cells, to make sure that the leads they get are relevant to physiopathological conditions.”
The government award may also enable Cisbio to better compete with its bigger rivals, which include PerkinElmer, Invitrogen, and DiscoverX, whose assay products are now distributed worldwide by GE Healthcare. Although Cisbio employs about 700 worldwide, its sales and marketing forces are dwarfed by these bigger companies.
Yet another goal of the project is to develop assay technology that is already compatible with a wide variety of existing readout equipment, Degorce said. Cisbio’s HTRF assays are currently validated on instruments from Tecan, BMG Labtech, and Molecular Devices. This validation process is ongoing, Degorce said, but it is time-consuming and has been a major difficulty in bringing variations of the HTRF assays to market.
“We would like our new technology to be able to be read on existing readers,” Degorce said. “We’ve been through this before, and it was a major hurdle being in a marketplace where the equipment was not ready, was not there, was not compatible, and we don’t particularly want to go through that again. So the idea behind all this is to make sure that the equipment already exists.”
To this end, Cisbio will likely experiment with readout instruments from several vendors beyond those it already has partnerships with. This in turn could lead to additional relationships with vendors regarding the company’s current HTRF product portfolio.
“Instrumentation has improved tremendously, and now because HTRF is well-received, more and more instrument manufacturers are coming to us asking for compatibility,” Degorce said. “It will be easier now to work with them and anticipate instrumentation, rather than be in a situation where only one or two instruments are compatible with this technology.”