CRISPR/Cas9 project discovers a better method to edit T cells

Kathrin Schumann

CRISPR/Cas9 tech and gene editing has emerged as a hot field in biotech, spurring a full slate of startups. Now one of the pioneers in the field has supervised a project that points to a more efficient use of technology in editing T cells.

Gene editing essentially involves doing surgery on DNA. The Cas9 enzyme is used as the blade, making the cut that can be used to insert new code. Working in a lab dish, Kathrin Schumann and Steven Lin assembled Cas9 ribonucleoproteins (RNPs) and then delivered them into the T cell after exposing them to an electrical field, making them more permeable.

By assembling the RNPs in advance, the team notes, they were able to more efficiently edit out CXCR4, which HIV uses to enter T cells, and PD-1, which cancer cells block in order to escape detection by the human immune system. Both are major targets in the drug development field.

"We tried for a long time to introduce Cas9 with plasmids or lentiviruses, and then to express separately the single-guide RNA in the cell," Schumann said. "Using RNPs made outside the cell, so that the cell is responsible for as little of the process as possible, has made a big difference."

Their work was overseen by the Innovative Genomics Initiative, which is a joint project undertaken by Berkeley and UCSF. Berkeley professor Jennifer Doudna, a pioneer behind CRISPR/Cas9 who founded Caribou Biosciences and outlicensed the tech to other biotechs, helped supervise along with Jonathan Weissman.

"Genome editing in human T cells has been a notable challenge for the field," says Alexander Marson, a senior author on the study. "So we spent the past year and a half trying to optimize editing in functional T cells. There are a lot of potential therapeutic applications, and we want to make sure we're driving this as hard as we can."

- here's the release
- get the research abstract

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