Systems Biology student Evan Daugharthy and George Church explain how fluorescent in situ sequencing works and describe potential applications, such as new diagnostics that could spot the earliest signs of disease

In biology, as in real estate, location matters. Working copies of active genes — called messenger RNAs or mRNAs — are positioned strategically throughout living tissues, and their location often helps regulate how cells and tissues grow and develop. But to analyze many mRNAs simultaneously, scientists have had to grind cells to a pulp, which left them no good way to pinpoint where those mRNAs sat within the cell.

Now a team at the Wyss Institute of Biologically Inspired Engineering at Harvard University and Harvard Medical School, in collaboration with the Allen Institute for Brain Science, has developed a new method that allows scientists to pinpoint thousands of mRNAs and other types of RNAs at once in intact cells — all while determining the sequence of letters, or bases, that identify them and reveal what they do.

The method, called fluorescent in situ RNA sequencing (FISSEQ), could lead to earlier cancer diagnosis by revealing molecular changes that drive cancer in seemingly healthy tissue. It could track cancer mutations and how they respond to modern targeted therapies, and uncover targets for safer and more effective ones.

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