Mann added, “This is a one-step process that avoids many of the risks associated with genome editing. The old way is problematic because cutting the genome is not perfectly efficient. Even when perfectly cut, the cell’s repair machinery does not always work as intended, resulting in further mutations to the DNA. This new platform is a big deal in terms of making therapies safer and more reliable.”

Mann, who wasn’t involved in the evoCAST study, commented about Witte’s time at the Institute, “The experience students get here equips them to contribute to high-impact discoveries later in their careers.”

“The Summer Scholars program was a fantastic introduction to science at the bench,” said Witte. “Working alongside Biff each day gave me the tools and confidence to help me develop as a young scientist.”

Witte’s team used a technique called phage-assisted continuous evolution (PACE) to refine the CAST system and dramatically boost its performance in human cells. The result was a 200- to 400-fold improvement in gene integration efficiency, with the ability to target dozens of human genomic sites and deliver therapeutic genes with high precision.

“In this study, we learned that the native activity of CAST was insufficient for genome editing in human cells,” said Witte. “However, we could remedy this through the directed evolution PACE technique.”

Mann sees clear relevance to the work happening across the Institute and at other research institutions. “Nearly every lab here and beyond relies on tools for genome editing,” he said. “New techniques like evoCAST could open doors to experiments — and insights — that weren’t previously possible.”