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A Method for the Acute and Rapid Degradation of Endogenous Proteins
Open accessAbstract
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.
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“The Trim-Away mechanism depletes target proteins directly at the protein level, bypassing limitations of transcriptional or RNA-targeting approaches and offering temporally precise control over protein levels.”
From Reverse the progression of Alzheimer’s disease through Nano-ERASER-based adult neuroregeneration (2026) · cites this paper as [21]
In the citing paper
“The longevity of TRIM-away efficacy was assessed to be roughly 3–4 days. However, this was dependent on the levels of target protein within cells, the amount of antibody being applied and the amount of TRIM21 within cells.”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [40]
In the citing paper
“The power of TRIM-away was also shown by its ability to target and degrade Rec8 in mouse oocytes within minutes [40].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [40]
In the citing paper
“As shown by targeting huntingtin, TRIM-Away was also able to distinguish between wild-type and mutant proteins, depending on the specificity of the delivered antibody [40].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [40]
In the citing paper
“The system could also be applied to primary cells, in which achieving protein silencing with RNAi or CRISPR/Cas9 is difficult.”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [40]
In the citing paper
“Using a GFP-specific antibody for microinjection into TRIM21 expressing cells, GFP levels were depleted with an apparent half-life of roughly 16 min [40].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [40]
In the citing paper
“To widen the applicability of the system beyond single cell analysis, the authors developed a bulk cell approach by using electroporation, showing specific effects on signalling pathways like ERK1 or mTOR [40].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [40]
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Metadata
- Authors
- Clift, D., McEwan, W. A., Labzin, L. I., Konieczny, V., Mogessie, B., James, L. C., & Schuh, M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Max Planck Institute for Biophysical Chemistry (DE)
- Corresponding author
- Clift, Dean
- James, Leo C.
- Schuh, Melina
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 171
- Issue
- 7
- Pages
- 1692-1706.e18
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5733393
- OpenAlex
- W2769995426
- Cited by
- 531
- References
- 65
- Citations by year
- 2026: 65 · 2025: 85 · 2024: 59 · 2023: 72 · 2022: 52 · 2021: 62 · 2020: 58 · 2019: 45 · 2018: 30 · 2017: 2
- FWCI
- 15.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion, cc-by)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Bristol Research (University of Bristol) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Medical Research Council (MC_U105192711, MC_U105181010)
- European Community’s Seventh Framework Programme (241548)
- European Research Council (ERC (337415)
- Wellcome Trust Investigator Award (200594/Z/16/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- mammalian cells, gene function analysis
- MeSH terms
- Animals, Antibodies, Biochemistry, Protein Transport, Proteolysis
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