Advanced Cell Diagnostics (ACD), originator of RNAscope® has named MicroMatrices’ their preferred partner for preclinical applications of RNAscope to assess on/off target effects of xenobiotic agents.
MicroMatrices has successfully developed a range of applications for this patented technology for detecting RNA in situ, to produce a unique target visualisation capability which can guide and/or corroborate mechanistic and mode of action studies , as well as aid target validation.
Detecting RNA in situ provides vital clues to a biomarker’s toxicological/clinical/biological relevance, unlike ‘grind and bind’ techniques e.g PCR, which lose cellular context, and IHC, which may not be reliable for thousands of genes, e.g . secreted proteins, receptors, GPCRs, ion channels, etc; in contrast, as much as 25% of genes can be successfully probed with RNAscope.
In recognition of their extensive experience and versatility in this area, ACD have endorsed MicroMatrices as their preferred partner for the development and/or delivery of preclinical applications of RNAscope®.
Examples of the ways in which the technology can be employed include:
MicroMatrices applies microarray-based analyses to derive a mechanistic hypothesis to explain how a chemical might be causing toxicity within a particular tissue. We then employ RNAscope to locate the changes to mechanistic biomarkers identified by arrays to a particular cell type or types in the tissue. This is important for corroboration of the array data and confirmation of the mechanism in the context of cellular function. This process can be applied retrospectively, using laser-dissected FFPE tissue, to enable product rescue based on the development of non human relevance arguments.
In order to facilitate the assessment of efficacy and the likelihood of “off target” or toxic effects, it is important to understand drug target distribution, particularly in the context of in vivo disease models. MicroMatrices have demonstrated skill in designing probes which will map drug targets across a broad range of tissues and across species, making it possible to visualise the distribution of drug targets in situ . In the drug development context, this valuable information can significantly assist in the choice of chemical candidates with more optimal efficacy and safety profiles.
In the constant search for new pharmaceuticals with a higher efficacy to safety ratio, novel methods for drug discovery are being developed, for example in silico compound design, or proteomics-based technology. These highly promising avenues to drug discovery require biological underpinning to provide early confirmation that the new agent is acting as expected. RNAscope can be used to develop phenotypic screens that furnish data showing that the drug is affecting the targets and/or pathways predicted.
on an interactive, step by step basis. Collaborations can begin with pilot projects which can then be scaled up to larger research programs, according to your requirements.