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Beyond Canonical PROTAC: Biological targeted protein degradation (bioTPD)
Huifang Wang,Runhua Zhou,Fushan Xu,Kongjun Yang,Liuhai Zheng,Pan Zhao,Guangwei Shi,Lingyun Dai,Chengchao Xu,Le Yu,Zhijie Li,Jianhong Wang,Jigang Wang 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Targeted protein degradation (TPD) is an emerging therapeutic strategy with the potential to modulate disease associated proteins that have previously been considered undruggable, by employing the host destructionmachinery. The exploration and discovery of cellular degradation pathways, including but not limited toproteasomes and lysosome pathways as well as their degraders, is an area of active research. Since the conceptof proteolysis-targeting chimeras (PROTACs) was introduced in 2001, the paradigm of TPD has been greatlyexpanded and moved from academia to industry for clinical translation, with small-molecule TPD being particularlyrepresented. As an indispensable part of TPD, biological TPD (bioTPD) technologies including peptide-, fusionprotein-, antibody-, nucleic acid-based bioTPD and others have also emerged and undergone significantadvancement in recent years, demonstrating unique and promising activities beyond those of conventional small molecule TPD. In this review, we provide an overview of recent advances in bioTPD technologies, summarize theircompositional features and potential applications, and briefly discuss their drawbacks. Moreover, we present somestrategies to improve the delivery efficacy of bioTPD, addressing their challenges in further clinical development.
Genetically Encoded Biosensor Engineering for Application in Directed Evolution
Mao Yin,Huang Chao,Zhou Xuan,Han Runhua,Deng Yu,Zhou Shenghu 한국미생물·생명공학회 2023 Journal of microbiology and biotechnology Vol.33 No.10
Although rational genetic engineering is nowadays the favored method for microbial strain improvement, building up mutant libraries based on directed evolution for improvement is still in many cases the better option. In this regard, the demand for precise and efficient screening methods for mutants with high performance has stimulated the development of biosensor-based highthroughput screening strategies. Genetically encoded biosensors provide powerful tools to couple the desired phenotype to a detectable signal, such as fluorescence and growth rate. Herein, we review recent advances in engineering several classes of biosensors and their applications in directed evolution. Furthermore, we compare and discuss the screening advantages and limitations of two-component biosensors, transcription-factor-based biosensors, and RNA-based biosensors. Engineering these biosensors has focused mainly on modifying the expression level or structure of the biosensor components to optimize the dynamic range, specificity, and detection range. Finally, the applications of biosensors in the evolution of proteins, metabolic pathways, and genome-scale metabolic networks are described. This review provides potential guidance in the design of biosensors and their applications in improving the bioproduction of microbial cell factories through directed evolution.