Geneticists have created an RNA "sensor" that finds and illuminates cancer cells
RNA-based "sensors" can help find cancer cells to deliver therapies. The study was published in the journal Nature Communications.Researchers at the Massachusetts Institute of Technology have developed an RNA-based sensor that can accurately identify cells expressing a mutated version of the cancer-specific p53 gene. "The sensors could be used to target cancer therapies.
Geneticists used an enzyme that is present in most animal cells, RNA-dependent adenosine deaminase (ADAR). It edits the bases of RNA molecules, converting mismatched adenosine bases into inosine. ADAR is typically used by cells to fight viruses: it detects and corrects mismatches in double-stranded RNA.
The researchers created a sensor RNA so that it contains a sequence complementary to their target (a molecule corresponding to the mutated p53 gene) but with one mismatch. This attracts the attention of ADAR, naturally existing in the cell, which eliminates this mismatch.
When ADAR converts adenosine to inosine in the sensor RNA, this edit removes the stop codon (a set of three nucleotides) that blocks RNA transcription. The cell then begins to read the genetic code and synthesize the proteins it encodes. One of these is a fluorescent protein, which allows us to see that the synthetic gene has been activated.
The other synthetic gene encodes a simplified version of the ADAR enzyme. As more ADAR is produced, the enzyme finds and activates more copies of the synthetic RNA construct. This creates a positive feedback loop that enhances fluorescent gene expression.
The researchers note that this approach can be used not only to identify cancer cells but also for treatment. The synthetic gene, which is contained in RNA, can encode more than just a fluorescent protein. As a "payload," such molecules can trigger the production of proteins that kill cancer cells.
"With this system, we can target very specific diseased cells and tissues, which opens up the possibility of identifying cancer cells and then delivering highly effective therapeutics," James Collins, professor of medical engineering and science and co-author of the study.
Source: Autocatalytic base editing for RNA-responsive translational control | Nature Communications