Transforming drug discovery with RNAscope™ Technology

How Concept Life Sciences Uses RNAscope™ to Advance Immuno-Oncology Drug Discovery

Concept Life Sciences is a leading contract research organisation, providing consultative drug discovery and development services to the global life sciences industry for over 25 years. Concept provides a broad range of early-stage drug discovery services in target identification as well as validation and RNAscope has become a key part of this offering, delivering a comprehensive understanding of RNA targets and their spatial arrangement within cells and tissue.

Dr. Giulia Tagliavini is a Senior Scientist in the Translational Biology team, where there is strong therapy area expertise in immunology, immuno-oncology and neurodegeneration. Giulia and her colleagues routinely leverage RNAscope and BaseScope™ assays to visualize RNA targets in tumor cells and immune cells in the spatial context of the tumor microenvironment. RNAscope brings significant advantages to immuno-oncology research, offering insights into the heterogeneity of complex tumor tissues and providing a means of quantifying RNA targets in fixed tumor samples.

“RNAscope enables us to locate and quantify the RNA target we are investigating, revealing valuable information on transcript abundance. It’s really helpful to be able to visualize the target and it's biodistribution.”

An Invaluable Resource for CROs And Their Clients

For CROs like Concept Life Sciences, RNAscope provides numerous benefits. Unlocking the spatial location of RNA targets is especially valuable for the drug discovery and development process, since it can reveal cell activity and key signaling events. Giulia noted the versatility of the platform from a CRO perspective:

“It certainly brings more advantages than traditional histology methods. As a CRO, we're always trying to stay at the forefront of drug development research, and part of that is offering the latest assays and cutting-edge technologies. We have found RNAscope to be a very robust assay that is easily applicable on so many different levels, across many different tissues and with a really broad offer of probes and targets.”

“We have also made use of RNAscope to validate antibodies, so it’s really a versatile tool for us. Overall, RNAscope allows us to gain unique insights into the spatial distribution of RNA targets, and helps us to deliver more robust results to our clients.”

Giulia also values the practicality and reproducibility of the assay:

“We do all our staining on a Leica Biosystems BOND RX Research Advanced Staining System, and Bio-Techne has a range of kits and probes designed for our platform. From my point of view, the assay is really straightforward – once you have your protocol set on the machine, it's really just a case of rinse and repeat. The results we get are always consistent and highly reproducible.”

Unlocking RNA-Protein Co-Detection

Expanding the possibilities of RNAscope further, Giulia has been developing the multiplex co-detection capabilities of the assay. By combining RNAscope ISH with traditional immunohistochemistry (IHC), Giulia and her colleagues have developed a protocol for visualizing RNA and protein targets on the same slide, significantly expanding the number of markers and cell activities that can be interrogated in a single assay. 

“I'm particularly interested in the visualization of protein and transcript on the same slide. This unlocks exciting possibilities, for example, being able to identify the original cells from which a protein was secreted from.”

Using the RNAscope 2.5 LS Assay-Red, Giulia developed a sequential 3-plex assay protocol in which RNAscope is first performed, followed by two rounds of IHC, to co-detect RNA and proteins in the same slide. This is highly useful for determining between tumor cells and specific leukocyte populations, while quantifying and determining the spatial distribution of RNA targets.

Figure 1: One of Giulia’s RNA-protein co-detection slides, showing target RNA in red, PanCK (cytokeratin marker) in brown, and CD3 (T-cell marker) in green.

“By adding an additional IHC step, we can highlight key protein markers for our immune-oncology projects, like PanCK, a pan marker for cytokeratins that is useful for identifying tumor regions, and of course, markers for distinct immune cell populations like CD3, CD20 and CD68. Being able to identify regions of tumor together with the RNA target really gives us more information for the image analysis stage.”

Future Prospects

With its ability to integrate RNA and protein detection, RNAscope is moving towards detecting more and more targets in a single slide. Thanks to the recent announcement of novel RNAscope protease-free protocols and reagents, multiomic co-detection with RNAscope is set to become substantially easier to detect protein and RNA in a single assay. By eliminating the proteases used for RNA detection, the advanced workflow prevents the degradation of protein and RNA while conserving tissue morphology. 

Giulia is currently seeking to incorporate fluorescence staining into her multiplex assays.

“Something we would like to try out is the RNAscope 2.5 LS Fluorescent Multiplex Assay, because while chromogenic staining is really good for visualizing distinct cell types, fluorescence might allow us to detect multiple RNA targets, or multiple protein targets in the same cell.”

Unwavering Support from A Trusted Partner

CROs like Concept Life Sciences can benefit from Bio-Techne’s expertise and support throughout their RNAscope journey.

“The support from Bio-Techne has always really been great. The initial training and setup I received was extremely thorough. They covered the theory of technology, how to troubleshoot, and how to use RNAscope on our Leica Biosystems BOND system. Since then, I have asked and relied on their knowledge and expertise during difficulties encountered in various projects, and they've always answered my questions, and offered advice on how to best proceed with the project.”

Bio-Techne can also help to design custom probes with a rapid turnaround time for time-sensitive projects. 

“When projects have demanded more specialized probes, Bio-Techne’s custom services have been brilliant. All we have to do is provide them with our target RNA sequence, and they get back to us with our custom probes in rapid time. It lets us provide a great level of flexibility in our services, which is great for us and our clients.”