Journal
CURRENT OPINION IN BIOTECHNOLOGY
Volume 78, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.copbio.2022.102807
Keywords
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Funding
- National Institutes of Health [R01EB029455]
- Department of Defense [W81WH-21-1-0892]
- National Science Foundation
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Targeted protein degradation (TPD) is a powerful tool for biological research and therapeutic development. It offers several advantages over functional inhibition alone, including the ability to target previously undruggable proteins and eliminate protein activity for an extended period. Biologics-based methods have expanded the TPD toolbox, allowing for depletion of extracellular and surface-exposed proteins with increased target specificity.
Targeted protein degradation (TPD) is a broadly useful proteome editing tool for biological research and therapeutic development. TPD offers several advantages over functional inhibition alone, including the ability to target previously undruggable proteins and the substantial and sustained knockout of protein activity. A variety of small molecule approaches hijack endogenous protein degradation machinery, but are limited to proteins with a cytosolic domain and suitable binding pocket. Recently, biologics-based methods have expanded the TPD toolbox by allowing access to extracellular and surface-exposed proteins and increasing target specificity. Here, we summarize recent advances in the use of biologics to deplete proteins through either the ubiquitin-proteasome system or the lysosomal degradation pathway, and discuss routes to their effective delivery as potential therapeutic interventions.
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