Advances in controllable targeted protein degradation: emerging strategies and mechanisms.

Xiaoding Ma, Jianli Yin, Fan Ding, Guo Han, Xingwan Liu, Haifeng Ye

Abstract readReview

In one paragraph

Review in Science China. Life sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Xiaoding MaShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Jianli YinShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Fan DingShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Guo HanShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Xingwan LiuShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Haifeng YeShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. hfye@bio.ecnu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Controllable targeted protein degradation (controllable TPD) technologies, exemplified by proteolysis-targeting chimeras (PROTACs), have emerged as transformative tools in drug discovery and molecular biology research. With the endogenous cellular degradation machinery, controllable TPD platforms allow for the precise targeting and regulated elimination of specific proteins within cells. Recent advances have expanded the spectrum of controllable degradation strategies, including photosensitive degrons, opto-PROTACs, auxin-inducible degron (AID) systems, small molecule-assisted shut-off (SMASh) techniques, and engineered E3 ubiquitin ligases such as ΔTRIM21 with enhanced targeted protein degradation efficiency (ΔTRIM-TPD). These emerging methodologies provide unprecedented control over protein stability, facilitating targeted therapeutic interventions for diseases such as cancer and infectious diseases, and significantly advancing fundamental biological research. This review systematically summarizes recent breakthroughs in controllable TPD strategies, elucidates their distinct molecular mechanisms, and highlights their promising therapeutic applications. The rapidly evolving field of controllable TPD represents a powerful and adaptable technological frontier, opening new avenues in precision medicine and providing versatile tools for the future of biomedical research.

Indexed as

ProteinsProteolysisAnimalsDrug DiscoveryHumansIndoleacetic AcidsUbiquitin-Protein LigasesIndoleacetic AcidsProteinsUbiquitin-Protein Ligasescancer therapycontrollable strategiesdrug discovery and developmentprecision medicinetargeted protein degradation

Identifiers

PMID41329322

DOI10.1038/s41392-024-02004-x

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.