AUTAB, a new technology for targeted degradation of cell membrane proteins based on autophagy

AUTAB (Autophagy-Targeting Antibody), a novel technology developed by researchers at the Shenzhen Institute of Advanced Technology (Chinese Academy of Sciences) to degrade cell membrane proteins without relying on third-party receptors (e.g., E3 ligases or lysosomal shuttling proteins).

AUTAB combines a polyethylenimine (PEI)-based autophagy-inducing module with a target-specific antibody. PEI's positive charge triggers membrane perturbation, activating the autophagy-lysosome pathway. The antibody directs the complex to specific membrane proteins (e.g., CD73), enabling selective degradation. Operates at nanomolar concentrations, achieving rapid and robust degradation across diverse cell types and membrane protein classes. Modular Nano-AUTAB systems enhance scalability and adaptability.

Advantages Over Existing Methods

• Receptor Independence: Eliminates reliance on endogenous receptors, reducing off-target effects.
• Broad Applicability: Targets traditionally "undruggable" membrane proteins (e.g., transporters, receptors).
• Precision: Minimal impact on non-target proteins.

Applications

• Cancer Therapy: Degrade immune checkpoint proteins (e.g., PD-L1) to enhance antitumor immunity.
• Neurological Disorders: Clear pathogenic transmembrane protein aggregates.
• Tool for Basic Research: Dynamically regulate membrane protein levels to study their functions.

Challenges & Future Directions

• Optimize in vivo delivery and stability of PEI-antibody conjugates.
• Assess long-term safety, particularly autophagy overactivation risks.
• Explore small-molecule ligands (as antibody alternatives) for cost-effective therapies.

AUTAB represents a paradigm shift in targeted protein degradation, offering a versatile platform for membrane protein research and therapeutic development. Its modular design and receptor-free mechanism hold promise for advancing precision medicine and tackling undruggable targets.

Reference

• Cheng, B., Li, M., Zheng, J. et al. Chemically engineered antibodies for autophagy-based receptor degradation. Nat Chem Biol (2025). https://doi.org/10.1038/s41589-024-01803-1