This image represents an infection-fighting cell called a neutrophil, in which the cell’s DNA is being “edited” to help restore its ability to fight bacterial invaders. Image credit: Illustration by Jill George using images from the National Human Genome Research Institute & the National Institute of Allergy and Infectious Diseases (CC BY-NC 2.0)
Humans are made up of many building blocks known as cells. The lives of cells are dynamic: they change what tasks they perform over time in response to cues from the rest of the body and the external environment. The mixture of proteins and other molecules present inside a cell, and how they interact with each other, influences how the cell behaves. There are many tools available to take snapshots of these molecules at specific moments, but few technologies that can measure them over periods of time.
A technology known as CRISPR genome editing enables researchers to modify the DNA of cells in a very precise and efficient way. It was adapted from a system that is naturally found in bacteria involving an enzyme called Cas9. Researchers design a molecule known as a guide ribonucleic acid (or guide RNA, for short) that binds to a specific location in the DNA of the cell. Cas9 then binds to the guide RNA and cuts the DNA at this location. When the cell repairs the cut, researchers can manipulate the repair process to make small edits to the DNA, or add or remove larger sections.
Choi et al. set out to develop a new method for recording when molecules within living cells interact using CRISPR-based tools. The records would be in the form of changes to the cells’ DNA that could be detected later using existing DNA sequencing technologies. The team split up the CRISPR guide RNA into two parts and attached extra RNA ‘adaptors’ to enable them to bind to two different proteins of interest. When the two proteins interacted with each other inside human kidney cells, the two halves of the guide RNA were brought together, and this enabled the guide RNA to drive specific editing of the cells’ DNA. Choi et al. dubbed this new approach P3 editing.
In the future, it may be possible to combine P3 editing with methods to record other aspects of cell biology into a cell’s DNA to reconstruct the history of that cell. One of the next steps following on from this work is to continue developing the P3 editing approach so that it can be more reliably delivered to cells and is more efficient at recording when molecules interact.
