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Targeted degradation of membrane and extracellular proteins with LYTACs

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Targeted degradation of membrane and extracellular proteins with LYTACs
Targeted protein degradation technology has gained substantial momentum over the past two decades as a revolutionary strategy for eliminating pathogenic proteins that are otherwise refractory to treatment.Among the various approaches developed to harness the body's innate protein homeostasis mechanisms for this purpose,lysosome targeting chimeras(LYTACs)that exploit the lysosomal degradation pathway by coupling the target proteins with lysosome-trafficking receptors represent the latest innovation.These chimeras are uniquely tailored to degrade proteins that are membrane-bound and extracellular,encompassing approximately 40％of all proteome.Several novel LYTAC formulas have been developed recently,providing valuable insights for the design and development of therapeutic degraders.This review delineates the recent progresses of LYTAC technology,its practical applications,and the factors that dictate target degradation efficiency.The potential and emerging trends of this technology are discussed as well.LYTAC technology offers a promising avenue for targeted protein degradation,potentially revolutionizing the therapeutic landscape for numerous diseases.

targeted protein degradationlysosome targeting chimeralysosome-trafficking receptorextracellular proteinmembrane protein

Yu-yang Li、Yang Yang、Ren-shuai Zhang、Rui-xin Ge、Song-bo Xie

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Department of Clinical Pathobiology and Immunological Testing,School of Medical Laboratory,Qilu Medical University,Zibo 255300,China

Translational Medicine Center,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China

Center for Cell Structure and Function,Shandong Provincial Key Laboratory of Animal Resistance Biology,Center for Cell Structure and Function,College of Life Sciences,Shandong Normal University,Jinan 250014,China

Department of Ophthalmology,Tianjin Medical University General Hospital,Ministry of Education International Joint Laboratory of Ocular Diseases,Tianjin Key Laboratory of Ocular Trauma,Tianjin Institute of Eye Health and Eye Diseases,China-UK"Belt and Road"Ophthalmology Joint Laboratory,Tianjin 300052,China

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targeted protein degradation lysosome targeting chimera lysosome-trafficking receptor extracellular protein membrane protein

2025

10.1038/s41401-024-01364-y

中国药理学报(英文版)
中科院上海药物研究所

中国药理学报(英文版)

影响因子：0.926
ISSN：1671-4083
年,卷(期)：2025.46(1)