Open Access

REVIEW

Recent biomedical advances enabled by HaloTag technology

WEIYU CHEN^1,2, MUHSIN H. YOUNIS³, ZHONGKUO ZHAO^1,*, WEIBO CAI^3,*

1 The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, China
2 International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, 322000, China
3 Departments of Radiology and Medical Physics, University of Wisconsin—Madison, Madison, WI, 53705, USA

* Corresponding Authors: Zhongkuo Zhao, ; Weibo Cai,

BIOCELL 2022, 46(8), 1789-1801. https://doi.org/10.32604/biocell.2022.018197

Received 16 July 2021; Accepted 02 December 2021; Issue published 22 April 2022

Abstract

The knowledge of interactions among functional proteins helps researchers understand disease mechanisms and design potential strategies for treatment. As a general approach, the fluorescent and affinity tags were employed for exploring this field by labeling the Protein of Interest (POI). However, the autofluorescence and weak binding strength significantly reduce the accuracy and specificity of these tags. Conversely, HaloTag, a novel self-labeling enzyme (SLE) tag, could quickly form a covalent bond with its ligand, enabling fast and specific labeling of POI. These desirable features greatly increase the accuracy and specificity, making the HaloTag a valuable system for various applications ranging from imaging to immobilization of POI. Notably, the HaloTag technique has already been successfully employed in a series of studies with excellent efficiency. In this review, we summarize the development of HaloTag and recent advanced investigations associated with HaloTag, including in vitro imaging (e.g., POI imaging, cellular condition monitoring, microorganism imaging, system development), in vivo imaging, biomolecule immobilization (e.g., POI collection, protein/nuclear acid interaction and protein structure analysis), targeted degradation (e.g., L-AdPROM), and more. We also present a systematic discussion regarding the future direction and challenges of the HaloTag technique.

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