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- CRISPR-Cas technologies: Emerging tools from research to clinical application
- Hana Hyeon, Soonhye Hwang, Yongyang Luo, Eunkyoung Shin, Ji-Hyun Yeom, Hong-Man Kim, Minkyung Ryu, Kangseok Lee
- J. Microbiol. 2025;63(8):e2504012. Published online August 31, 2025
- DOI: https://doi.org/10.71150/jm.2504012
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Abstract
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CRISPR-Cas technologies have emerged as powerful and versatile tools in gene therapy. In addition to the widely used SpCas9 system, alternative platforms including modified amino acid sequences, size-optimized variants, and other Cas enzymes from diverse bacterial species have been developed to apply this technology in various genetic contexts. In addition, base editors and prime editors for precise gene editing, the Cas13 system targeting RNA, and CRISPRa/i systems have enabled diverse and adaptable approaches for genome and RNA editing, as well as for regulating gene expression. Typically, CRISPR-Cas components are transported to the target in the form of DNA, RNA, or ribonucleoprotein complexes using various delivery methods, such as electroporation, adeno-associated viruses, and lipid nanoparticles. To amplify therapeutic efficiency, continued developments in targeted delivery technologies are required, with increased safety and stability of therapeutic biomolecules. CRISPR-based therapeutics hold an inexhaustible potential for the treatment of many diseases, including rare congenital diseases, by making permanent corrections at the genomic DNA level. In this review, we present various CRISPR-based tools, their delivery systems, and clinical progress in the CRISPR-Cas technology, highlighting its innovative prospects for gene therapy.
- Interaction between the α-Barrel Tip of Vibrio vulnificus TolC Homologs and AcrA Implies the Adapter Bridging Model
- Seunghwa Lee , Saemee Song , Minho Lee , Soonhye Hwang , Ji-Sun Kim , Nam-Chul Ha , Kangseok Lee
- J. Microbiol. 2014;52(2):148-153. Published online February 1, 2014
- DOI: https://doi.org/10.1007/s12275-014-3578-2
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- 11 Crossref
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Abstract
- The AcrAB-TolC multidrug efflux pump confers resistance to Escherichia coli against many antibiotics and toxic compounds. The TolC protein is an outer membrane factor that participates in the formation of type I secretion systems. The genome of Vibrio vulnificus encodes two proteins homologous to the E. coli TolC, designated TolCV1 and TolCV2. Here, we show that both TolCV1 and TolCV2 partially complement the E. coli TolC function and physically interact with the membrane fusion protein AcrA, a component of the E. coli AcrAB-TolC efflux pump. Using site-directed mutational analyses and an in vivo cross-linking assay, we demonstrated that the α-barrel tip region of TolC homologs plays a critical role in the formation of functional AcrAB-TolC efflux pumps. Our findings suggest the adapter bridging model as a general assembly mechanism for tripartite drug efflux pumps in Gram-negative bacteria.
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Citations
Citations to this article as recorded by
- Functions and Regulation of the Outer Membrane Protein TolC in Vibrio Species
Yue Gong, Chunxia Liu, Xin Tian, Young Ran Kim
ACS Infectious Diseases.2025; 11(7): 1756. CrossRef - Progress of Antimicrobial Mechanisms of Stilbenoids
Xiancai Li, Yongqing Li, Binghong Xiong, Shengxiang Qiu
Pharmaceutics.2024; 16(5): 663. CrossRef - Membrane Efflux Pumps of Pathogenic Vibrio Species: Role in Antimicrobial Resistance and Virulence
Jerusha Stephen, Manjusha Lekshmi, Parvathi Ammini, Sanath H. Kumar, Manuel F. Varela
Microorganisms.2022; 10(2): 382. CrossRef - TolCV1 Has Multifaceted Roles During Vibrio vulnificus Infection
Yue Gong, Rui Hong Guo, Joon Haeng Rhee, Young Ran Kim
Frontiers in Cellular and Infection Microbiology.2021;[Epub] CrossRef - Recent paradigm shift in the assembly of bacterial tripartite efflux pumps and the type I secretion system
Inseong Jo, Jin-Sik Kim, Yongbin Xu, Jaekyung Hyun, Kangseok Lee, Nam-Chul Ha
Journal of Microbiology.2019; 57(3): 185. CrossRef - NaCl promotes antibiotic resistance by reducing redox states in Vibrio alginolyticus
Jun Yang, Zao‐Hai Zeng, Man‐Jun Yang, Zhi‐Xue Cheng, Xuan‐Xian Peng, Hui Li
Environmental Microbiology.2018; 20(11): 4022. CrossRef - ATP-Binding Cassette Transporter VcaM from Vibrio cholerae is Dependent on the Outer Membrane Factor Family for Its Function
Wen-Jung Lu, Hsuan-Ju Lin, Thamarai Janganan, Cheng-Yi Li, Wei-Chiang Chin, Vassiliy Bavro, Hong-Ting Lin
International Journal of Molecular Sciences.2018; 19(4): 1000. CrossRef - Functional analysis of Vibrio vulnificus RND efflux pumps homologous to Vibrio cholerae VexAB and VexCD, and to Escherichia coli AcrAB
Seunghwa Lee, Ji-Hyun Yeom, Sojin Seo, Minho Lee, Sarang Kim, Jeehyeon Bae, Kangseok Lee, Jihwan Hwang
Journal of Microbiology.2015; 53(4): 256. CrossRef - Molecular architecture of the bacterial tripartite multidrug efflux pump focusing on the adaptor bridging model
Saemee Song, Jin-Sik Kim, Kangseok Lee, Nam-Chul Ha
Journal of Microbiology.2015; 53(6): 355. CrossRef - Interaction Mediated by the Putative Tip Regions of MdsA and MdsC in the Formation of a Salmonella-Specific Tripartite Efflux Pump
Saemee Song, Soonhye Hwang, Seunghwa Lee, Nam-Chul Ha, Kangseok Lee, Eric Cascales
PLoS ONE.2014; 9(6): e100881. CrossRef - Functional Analysis of TolC Homologs in Vibrio vulnificus
Seunghwa Lee, Saemee Song, Kangseok Lee
Current Microbiology.2014; 68(6): 729. CrossRef
- Functions and Regulation of the Outer Membrane Protein TolC in Vibrio Species
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