Goals and Approach

The Write Team develops CRISPR-based tools that record cellular events into the DNA of the cell. Such records can include information on cellular lineages, internal occurrences and decisions, external signals or stressors, phenotypic changes, and, in theory, any biological signal. Importantly, this information is recorded sequentially. This creates a relative timeline of each event as it happens, acting like a cellular smart watch that can later report back on the health, actions, and experiences of the cell. 

To accomplish this, team members use DNA Typewriter. A synthetic DNA sequence, called a Tape, is installed into a cell’s genomic DNA. The first segment of Tape is nicked using a CRISPR-Cas9 enzyme. A short DNA sequence, known as a molecular barcode, is then inserted into the cut site. The barcodes function similar to the Morse Code, where each unique barcode translates to a specific cellular event. Thus, the insertion of the barcode into the DNA creates a record of a specific event. 

Once the first segment of Tape has a barcode inserted, the second segment opens for modification. This enables an orderly, sequential insertion of barcodes. Later, scientists can read the barcoded record in the Tape to find out what events took place in the cell and the order in which they occurred. 

DNA Typewriter technology will reveal the events of cellular biology with  unprecedented resolution. Prior approaches mainly relied on collecting discontinuous information at multiple time points to infer the history of cellular events. DNA Typewriter is beginning to enable scientists to obtain continuous records of past cellular events by decoding information written in the Tapes, just like information collected on a smart watch.