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Updated: Aug 6, 2026
05:33
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Published on: November 9, 2020
RNA-based ATTEC: an RNA-guided autophagy-lysosome platform for targeted protein degradation
Yunqiu Zhang1, Wanting Yang1, Yan Xu1
1Bioresource Utilization Center, Chengdu Institute of Biology, Chinese Academy of Science, Chengdu 610213, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Bioorganic & Medicinal Chemistry
|July 22, 2026
Summary
Researchers developed a new RNA aptamer-based strategy called autophagosome-tethering compound (ATTEC) to expand targeted protein degradation (TPD) beyond small molecules. This versatile platform enables degradation of various proteins, including transcription factors and oncoproteins.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Targeted protein degradation (TPD) is a rapidly advancing field in drug discovery.
- Current TPD methods using small molecules have limitations in targeting diverse proteins.
- Expanding TPD to a wider range of proteins is crucial for biomedical research.
Purpose of the Study:
- To introduce a novel RNA aptamer-based autophagosome-tethering compound (ATTEC) strategy.
- To overcome the limitations of small-molecule ligands in targeted protein degradation.
- To demonstrate the versatility and programmability of the ATTEC platform for novel drug discovery.
Main Methods:
- Designed a heterobifunctional molecule (GWD) to recruit LC3 to an RNA aptamer scaffold.
- Utilized genetically encoded tandem aptamer RNA scaffolds for target recognition.
- Employed modular replacement of aptamer units to target different proteins.
Main Results:
- Achieved efficient degradation of multiple transcription factors (E2F1, p50, p65) by modular aptamer replacement.
- Demonstrated targeted degradation of RNA-binding protein RBFOX1 and oncoprotein EGFR in HeLa cells.
- Validated the ATTEC platform as a versatile tool for protein degradation.
Conclusions:
- The aptamer-based ATTEC platform offers a modular and programmable approach to targeted protein degradation.
- This strategy significantly expands the scope of targetable proteins for therapeutic and research applications.
- ATTEC holds substantial promise for advancing innovative drug discovery and fundamental biological research.
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