How can you write data to DNA without changing the base sequence?

A new method lets anyone with a kit write data to DNA with just one enzyme.

Zettabytes—that’s 10²¹ bytes—of data are currently generated every year. All of those cat videos have to be stored somewhere, and DNA is a great storage medium; it has amazing data density and is stable over millennia.

To date, people have encoded information into DNA the same way nature has, by linking the four nucleotide bases comprising DNA—A, T,  C, and G—into a particular genetic sequence. Making these sequences is time-consuming and expensive, though, and the longer your sequence, the higher chance there is that errors will creep in.

But DNA has an added layer of information encoded on top of the nucleotide sequence, known as epigenetics. These are chemical modifications to the nucleotides, specifically altering a C when it comes before a G. In cells, these modifications function kind of like stage directions; they can tell the cell when to use a particular DNA sequence without altering the “text” of the sequence itself. A new paper in Nature describes using epigenetics to store information in DNA without needing to synthesize new DNA sequences every time.

Typesetting with DNA

The technique uses a long strand of DNA with a set sequence—the template—and a bunch of shorter, premade DNA molecules that can base pair with specific spots on the template—the bricks. Some of the bricks contain epigenetically modified Cs, and some don’t. When a modified brick base pairs with its designated spots on the template, it acts as a signal for an enzyme to modify that spot on the template DNA strand as well, “printing” the epigenetic information onto it without any new DNA synthesis—kind of like setting movable type.

This works because the modified site (a CG) will base pair with a GC on its opposite strand. But since that opposite strand runs in the other orientation, it will also look like a CG to the enzymes that make the modification.

The developers of the system call each of these potentially modifiable spots on the template an epi-bit, with the modified version corresponding to a 1 in a conventional computer bit and the unmodified version corresponding to a 0. Because no synthesis is required, multiple bits can be written simultaneously. To read the information, the scientists rigged the system so that 1s fluoresce and 0s don’t. The fluorescence, along with the sequences of bases, was read as the DNA was passed through a tiny pore.

Pictures in a meta-genome

Using this system, Zhang et al. created five DNA templates and 175 bricks to record 350 bits at a time. Using a collection of tagged template molecules, the researchers could store and read roughly 275,000 bits, including a color picture of a panda’s face and a rubbing of a tiger from the Han dynasty, which ruled China from 202 BCE to 220 CE.

They then had 60 student volunteers “with diverse academic backgrounds” store texts of their choice in epi-bits using a simple kit in a classroom. Twelve of the 15 stored texts were read successfully.

We’re not quite ready for your cat videos yet, though. There are still errors in the printing and reading steps, and since these modifications don’t survive when DNA is copied, making additional versions of the stored information may get complicated. Plus, the stability of these modifications under different storage conditions remains unknown, although the authors note that their epi-bits stayed stable at temperatures of up to 95o° C.

But once these and a few other problems are solved—and the technology is scaled up, further optimized and automated, and/or tweaked to accommodate other types of epigenetic modifications—it will be a clever and novel way to harness natural data storage methods for our needs.

Nature, 2024.  DOI: 10.1038/s41586-024-08040-5

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