Researchers at MIT have developed an RNA sensor that can accurately
Geneticists have used an enzyme thatpresent in most animal cells, RNA-dependent adenosine deaminase (ADAR). It edits the bases of RNA molecules, converting mismatched adenosine bases into inosine. Typically, ADAR is used by cells to fight viruses: it detects and corrects mismatches in double-stranded RNA.
Researchers create sensor RNAso that it contains a sequence that is complementary to their target (the molecule corresponding to the mutated p53 gene), but with one mismatch. This draws the attention of ADAR, which naturally exists in the cell, which eliminates this discrepancy.
When ADAR converts adenosine to inosinesensor RNA, this editing removes a stop codon (a set of three nucleotides) that blocks RNA transcription. After that, the cell begins to read the genetic code and synthesize the proteins that it encodes. One of them is a fluorescent protein that allows you to see that a synthetic gene has been activated.
Another synthetic gene encodes a simplifiedversion 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 the expression of the fluorescent gene.
The researchers note that this approach canbe used not only for the identification of cancer cells, but also for treatment. The synthetic gene contained in RNA can code for more than just a fluorescent protein. As a payload, such molecules can trigger the production of cancer-killing proteins.
With this system, we can targetvery specific diseased cells and tissues, which opens up the possibility of identifying cancer cells and then delivering highly effective therapeutic agents.
James Collins Professor of Medical Engineering and Science and study co-author
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