RNA and protein co-detection in tissue samplesISH-IHC CRO services to quantify both RNA and protein on the same tissue section, retaining the spatial and morphological context.
Measuring RNA and protein together links transcription to protein expression. Our ISH-IHC CRO services bring that view to many programs, such as targeted protein degradation, RNA therapeutics, and immuno-oncology.
For cell and gene therapy programs, it is especially valuable with gene editing constructs: you see which cells express the editor, whether transcript and protein colocalize, and how both are distributed across the tissue.
Cas mRNA and protein mapped to individual myofibers and myonuclei, from staining to quantitative results.
What you learn when RNA and protein are read together
Choose a research area to see the type of questions our ISH-IHC CRO services help answer. The schematic shows examples of what you are able to quantify if you target: RNA only, protein only, and both.
Cell and gene therapy
Which cells express the transgene or editor, and is it being made into protein?
After delivery, expression varies from cell to cell and from region to region. Reading the construct’s mRNA and protein together shows where it is expressed and whether it is translated.
- Bulk sequencing
- Average expression or editing for the whole sample, with no location.
- RNA alone
- Which cells transcribe the construct.
- Protein alone
- Where the protein is. In muscle, protein can spread along a fiber away from the nucleus that made it.
- RNA + protein, one section
- mRNA and protein linked in each fiber and nucleus, with a map of how expression varies across the tissue.
Targeted protein degradation
Is the drug degrading the target protein, and in which cells?
A degrader should remove the protein and leave its mRNA in place. Reading both in the same cells shows whether protein loss comes from degradation, and where protein remains.
- Bulk sequencing
- mRNA averaged over the whole sample. No protein measurement.
- RNA alone
- Which cells make the target mRNA.
- Protein alone
- Where protein dropped, but not whether the cell also stopped making the mRNA.
- RNA + protein, one section
- mRNA present and protein gone in the same cell: degradation, confirmed cell by cell.
RNA therapeutics
Did the drug reach the target cells, and has the protein dropped yet?
siRNA and antisense drugs lower the target mRNA first. Protein follows as it turns over. Reading both shows which cells were reached and whether protein has caught up.
- Bulk sequencing
- Average knockdown for the whole sample, with all cell types mixed together.
- RNA alone
- Which cells lost the mRNA and which kept it.
- Protein alone
- Where protein remains, but not why.
- RNA + protein, one section
- Separates cells where protein is still clearing from cells the drug never reached.
Immuno-oncology
Which immune cells are active, and where are they in the tumor?
Cytokines such as IFNG are secreted, so their protein is hard to trace back to a cell. The mRNA marks the cell that makes it, and protein markers tell you what kind of cell it is.
- Bulk sequencing
- Cytokine levels for the whole sample, with no cell type or location.
- RNA alone
- Which cells make the cytokine, but not what type they are.
- Protein alone
- Where T cells are, but not whether they are active.
- RNA + protein, one section
- Active T cells identified and mapped to the tumor core, margin, and stroma.
ISH-IHC CRO services designed for your research question
Our scientists help you pick the platform and technologies that fit your research question.
Choose the ISH chemistry
We use Molecular Instruments or ACD technology, whichever detects your target better and is more reproducible for that target.
Design and optimize the assay
We design and optimize assays to run on Roche Ventana, Leica BOND, or Biocare automated systems.
Glint Lab is listed as a Biocare CRO partner.
Image and analyze
Whole slide imaging and automated image analysis turn each slide into quantitative and actionable data for each phenotype as well as their spatial interplay within the tissue context.
Spatially mapping Cas mRNA and protein to individual myofibers and myonuclei
The Gene therapy research is performed by Mammoth Biosciences. Glint Lab performed multiplex RNAscope ISH, immunofluorescence, and automated image analysis on muscle samples received from Mammoth Biosciences.
ISH-IHC CRO services performed at Glint Lab
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