How DNA is read: Future

gene expression in single cells
Fibroblast cell. Image by Heiti Paves via Wikimedia Commons.

In my novel, Thirty, people have an annual health scan that reads the levels of their genes and corrects these to normal levels so that they can stay young and healthy forever.

Unfortunately real science hasn’t yet caught up. We are, however, one step closer because it is now possible to measure gene expression in cells by looking at them. 

Scientists did this with a new technology called MERFISH which uses fluorescent probes to label single RNA molecules. Our DNA encodes all our genes and all the extra regulatory material needed to control when and where those genes are expressed. Genes are sequences of DNA that can be used to make the proteins that are needed for our cells to function. For DNA to be made into proteins, it is first transcribed into RNA which is then translated into protein. The amount of RNA from a particular gene in a cell tells us how much that gene is being used. This is different in every cell type i.e. skin cells use different genes to liver cells etc. It also changes over each 24 hour cycle and is different in healthy and diseased tissues.

That’s why we use RNA levels to measure gene expression in different disease models. We want to see which genes are contributing to that disease. We can now do this in single cells by processes called quantitative PCR or genome sequencing. In both these techniques the cell is destroyed as RNA is extracted so we can’t see where in the cell each different RNA was. A single cell only has a very small amount of RNA, so to be able to quantify it with either of these techniques, we first need to amplify it. This step can introduce a bias as more abundant RNAs are amplified more efficiently than less abundant RNAs.

MERFISH avoids both these problems because it shows exactly where the RNAs are in the cell, which other RNAs they are near and also does not require amplification. It works by labelling RNA with probes. One end of each probe binds to a particular RNA and the other end binds to a fluorescent protein. Each RNA is bound with a unique combination of probes so it will bind to a specific combination of fluorescent labels. The fluorescence is then read using a microscope and used to decode the underlying bound RNA. Using this system, scientists were able to decode 80% of the fluorescent spots correctly.

Fluorescence has been used before to measure RNA levels, but only for 30 different RNAs at a time. MERFISH can measure thousands of different RNAs from thousands of different genes in one cell. This will allow scientists to work out which genes are working together to cause various diseases.

Unfortunately MERFISH only works in cells that have been fixed with formaldehyde. So it can’t be used yet to create the kind of scanner that treats people in my story.

The Scientific Paper:

Chen et al. Spatially resolved, highly multiplexed RNA profiling in single cells. Science. 2015.

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