Deprived of one of its proteins, a cell may betray the protein’s function—but not always. If the cell is deprived of the protein indirectly, at the level of protein-coding DNA or RNA (that is, via CRISPR/Cas9 knockout or RNA interference [RNAi] knockdown), the cell will experience a deficit only after many hours or even days have passed. The cell may have time to develop mechanisms to compensate for the loss of a protein. And so, the cell may effectively hide the protein’s function, particularly if the protein is long-lived.
To assess protein function more directly—and quickly—scientists based at the Medical Research Council (MRC) in the U.K. and the Max Plank Institute (MPI) in Germany developed a new technique. It’s called Trim-Away. Unlike CRISPR/Cas9 and RNAi, it can deplete a targeted protein from any cell type, including nondividing primary cells, which resist DNA- and RNA-targeting techniques. Also, Trim-Away can distinguish between different variants of a protein, opening new paths to disease research or even, eventually, the development of new therapies.
Details about Trim-Away appeared November 16 in the journal Cell, in an article entitled “A Method for the Acute and Rapid Degradation of Endogenous Proteins.” The article emphasizes that because Trim-Away utilizes antibodies, it can be applied to a wide range of target proteins using off-the-shelf reagents.
“Here, we present Trim-Away, a technique to degrade endogenous proteins acutely in mammalian cells without prior modification of the genome or mRNA,” wrote the article’s authors. “Trim-Away harnesses the cellular protein degradation machinery to remove unmodified native proteins within minutes of application.”
Unlike CRISPR Knockout and RNAi Knockdown, Trim-Away Depletes Proteins Straightaway
