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Shipman lab pioneers more efficient genome editing
New technique poised to advance research from bacteria to humans
By Katherine Krebs / Wed Jan 5, 2022
The UCSF Department of Bioengineering and Therapeutic Sciences (BTS) is proud to announce the Shipman Lab’s newest publication, “Precise genome editing across kingdoms of life using retron-derived DNA,” released on December 23, 2021 in Nature Chemical Biology.
Senior author Seth Shipman, PhD, explained:
In this work, we use bacterial elements known as retrons to improve precise genome editing. In bacteria, retrons help defend cells against viruses, in part by producing a short fragment of reverse transcribed DNA. We modify retrons so that they create a segment of reverse transcribed DNA that is almost identical to a cell’s genome, but contains a small change that we want to introduce. This reverse transcribed DNA can serve as a template for genome editing, when combined with additional editing materials (e.g. a recombinase in bacteria, or Cas9 and a gRNA in yeast and human cells).
Notably, we show that this strategy of using retron-derived DNA templates to introduce precise changes is a versatile platform technology, useful in bacteria, yeast, and even human cells. We also show that we can make modifications to the retron that increase the amount of DNA that is created in cells. These modifications also increase the rate of precise editing, showing that the abundance of template DNA is a limiting factor in genome editing. The advances here will hopefully one day be incorporated into human therapeutics to treat genetic disease, and will immediately enable us to better modify cells in the lab to understand the fundamental biology of disease.
Shipman is a faculty member in BTS and an assistant investigator at the Gladstone Institutes.
Additional authors include Santiago C. Lopez, Kate D. Crawford, Sierra K. Lear, and Santi Bhattarai-Kline.
The Shipman Lab is understandably excited and described this as “their first real publication.” Congratulations to all!
About the School: The UCSF School of Pharmacy aims to solve the most pressing health care problems and strives to ensure that each patient receives the safest, most effective treatments. Our discoveries seed the development of novel therapies, and our researchers consistently lead the nation in NIH funding. The School’s doctor of pharmacy (PharmD) degree program, with its unique emphasis on scientific thinking, prepares students to be critical thinkers and leaders in their field.