A Method for the Acute and Rapid Degradation of Endogenous Proteins

Dean Clift, William A McEwan, Larisa I Labzin, Vera Konieczny, Binyam Mogessie, Leo C James, Melina Schuh

Research output: Contribution to journalArticle (Academic Journal)peer-review

170 Citations (Scopus)
277 Downloads (Pure)


Methods for the targeted disruption of protein function have revolutionized science and greatly expedited the systematic characterization of genes. Two main approaches are currently used to disrupt protein function: DNA knockout and RNA interference, which act at the genome and mRNA level, respectively. A method that directly alters endogenous protein levels is currently not available. Here, we present Trim-Away, a technique to degrade endogenous proteins acutely in mammalian cells without prior modification of the genome or mRNA. Trim-Away harnesses the cellular protein degradation machinery to remove unmodified native proteins within minutes of application. This rapidity minimizes the risk that phenotypes are compensated and that secondary, non-specific defects accumulate over time. Because Trim-Away utilizes antibodies, it can be applied to a wide range of target proteins using off-the-shelf reagents. Trim-Away allows the study of protein function in diverse cell types, including non-dividing primary cells where genome- and RNA-targeting methods are limited.

Original languageEnglish
Pages (from-to)1692-1706.e8
Number of pages34
Issue number7
Early online date16 Nov 2017
Publication statusPublished - 14 Dec 2017


  • Journal Article


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