The Future of DNA Editing: DNA Typewriting

A revolutionary approach to recording cellular events

The future of medical research relies on being able to track and record what is going on inside of our cells, and DNA typewriting promises to do just that. So what is DNA typewriting, and how does it work? Well, the analogy of a typewriter is actually a bit of a stretch. The name mostly refers to the ability to record cellular information in a specific order, unlike other DNA-editing methods, which typically are not able to record sequential information with precision (1). This unique ability makes DNA typewriting a powerful tool with the potential to help us obtain a better understanding of many diseases.

DNA typewriters help record information about a cell in the non-coding (unused) parts of the cell’s DNA (1). By using over 4,000 barcodes, DNA typewriters can keep track of almost anything in the cell’s history, including the sequence of cell divisions, genetic modifications or mutations, and interactions with other cells (2). DNA typewriting works by embedding unique barcodes and recording the sequence and timing of events that occur within the individual cells. Afterwards, scientists can read that information from the cell’s DNA. This technique helps researchers track cells through their development and observe how they develop over time within the larger organism (2).

DNA typewriting embeds the relevant information into DNA using a technique called prime editing. Prime editing is based on CRISPR, a tool that allows scientists to make specific changes to DNA. CRISPR works like molecular scissors, cutting the DNA and allowing pieces of genetic material to be removed, added, or changed. While CRISPR relies on the cell’s repair mechanisms, which are less accurate, prime editing is much more reliable. It can make a wider variety of changes, including substitutions, insertions, and small deletions, by carefully changing the DNA sequence using the template at a targeted location (3). This precision makes prime editing more convenient and allows scientists to record a cell’s history accurately and with a low risk of unintended mutations.

Although DNA typewriters are still very new, they have plenty of potential to reshape medical research in the future. For example, scientists at MIT are currently developing ways to enhance cancer research using this new technology. They are using DNA typewriters to track how normal lung cells morph into cancer cells and then progress into tumors. Dr. Yang, a scientist at MIT, says DNA typewriting “suddenly gave us unprecedented resolution to understand how you go from one cancer cell all the way to this diverse, aggressive collection of tumor cells.” So far, they have surprisingly found that chemical changes to the DNA, not differences in the sequence itself, drive the spread of cancer. (4)

Overall, DNA typewriting reshapes the way that we understand cell evolution. With unprecedented precision and accuracy, it holds the potential to do far more than just editing DNA. Scientists are already making new discoveries about diseases like cancer using DNA typewriters, and there is no telling what could come next.

Bibliography:

  1. Liao H, Choi J, Shendure J. (2024, Jun 6) Molecular recording using DNA Typewriter. Nature Protocols. Retrieved from https://pubmed.ncbi.nlm.nih.gov/38844553/
  2. Allen Institute. (2024, January 8). DNA Typewriter Keeps a Record of Cells’ Long Histories. Allen Institute. https://alleninstitute.org/news/dna-typewriter-keeps-a-record-of-cells-long-histories/
  3. Chen P, Liu D. (2022, Nov 7) Prime editing for precise and highly versatile genome manipulation. Nature Reviews. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC10989687/#fn-group1
  4. Williams, S. (2024, Nov 15) Recording Cancer Cells from the Inside. Columbia University Irving Medical Center. Retrieved from https://www.cuimc.columbia.edu/news/dian-yang-recording-cancer-cells-inside?u

Images: 

https://alleninstitute.org/wp-content/uploads/2023/01/dna_typewriter-01_copy_web-scaled.jpg

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