CAMERA Offers a Snapshot of Your DNA
When CRISPR was discovered less than a decade ago, scientists worldwide rejoiced at the ease with which they could now target and alter DNA. It has become apparent, however, that gene editing isn’t the only trick up CRISPR’s sleeve.
CRISPR’s editing mechanism is simple yet elegant. In the cell, guide RNA (gRNA) molecules locate and bind to specific DNA sequences. The gRNA is linked to Cas9, an enzyme which cuts the targeted DNA strands, effectively deleting or modifying genetic material in living organisms.
Harvard researchers David Liu and Weixin Tang recently adapted this mechanism to serve a different purpose. Their study, published in Science, details a device called CRISPR-mediated analog multi-event recording apparatus (CAMERA). Using CRISPR-cas9’s modification mechanism, Liu and Tang gave CAMERA the ability to record a variety of cellular experiences such as exposure to light, antibiotics, and viral infection.
CAMERA fills a major hole in biochemical research, according to Liu. “There are a lot of questions in cell biology where you’d like to know a cell’s history,” he says, referring to environmental factors or internal signalling defects which can lead to cancer.
He hopes to gain insight into cell processes such as aging, environmental changes, and embryonic development. CAMERA can document not only the presence of a stimulus but also its strength and duration in populations as small as 10-100 cells.
Liu and Tang essentially developed two different “CAMERA”s. CAMERA1 operates only in prokaryotes and requires a small signal to generate reliable data. Two of its recorder plasmids (R1 and R2) are taken up by the cell in equal ratios. Then, after exposure to a stimulus, an R1 selective CRISPR-cas9 complex destroys the plasmid. By measuring the ratio of R1 to R2 at the end of the experiment, researchers can measure the duration of stimulus exposure.
CAMERA2 is more compelling since it also functions in humans, not just bacteria. Unlike CAMERA1’s entire sequence deletions, CAMERA2’s cas9 enzyme edits single base pairs of the target DNA or “harbor gene.” The duration of stimulus exposure directly correlates to the number of edits in the harbor gene.
“We set out to turn changes in a cell’s state into permanent changes in its DNA,” says Liu. But what he and Tang have created has implications beyond the human body. In the future, the CAMERA technique could be applied to developing biological environmental sensors which record the presence of pollutants globally.
One thing is certain: we are far from discovering all that CRISPR has to offer.