• Recent advances in genome engineering by CRISPR technology

    Mechanisms of target and off-target DNA recognition and cleavage of CRISPR-Cas effectors. (A) Top: Schematic diagram of the structure and full domain of the CRISPR-Cas9 protein. In the figure, each inset represents the interaction between the Cas9 domain and PAM distal region (left inset) and the PAM proximal region (right inset) within the guide RNA-DNA heteroduplex. Bottom: Schematic diagram of the interaction between guide RNA-target DNA heteroduplex and CRISPR-Cas9 protein. (B) Top: Schematic diagram of the structure and full domain of the CRISPR-Cas12a protein. In the figure, each inset represents the interaction between the Cas12a domain and PAM proximal region (left inset) and PAM distal region (right inset) within the crRNA-DNA heteroduplex. Bottom: Schematic diagram of the interaction between the guide RNA-target DNA heteroduplex and the CRISPR-Cas12a protein. NTS: non-target strand, TS: target strand, REC: Recognition domain, RuvC: RuvC domain, PI: PAM interaction domain, WED: Wedge domain, Nuc: Nuclease domain. The structures (A, B) are obtained from Protein Data Bank (PDB) and molecular images of SpCas9 (A, PDB: 7QQS) and FnCas12a (B, PDB: 6I1K) were illustrated using PyMOL software (The PyMOL Molecular Graphics System, Version 2.5.4 Schrödinger, LLC.). (C) Schematic diagram of the cleavage mechanism of CRISPR-Cas9 (Top) and Cas12a (Bottom) effectors for on-target and off-target DNA. Red arrowhead: cleavage of DNA. Red triangles: Mismatched sequence between guide RNA and target DNA. Images were created with BioRender.com.
  • Mitochondrial genome editing: strategies, challenges, and applications

    mtDNA editing approaches. (Middle) Mitochondrial heteroplasmy and threshold effect of disease onset. The concept of mitochondrial heteroplasmy and its relationship to the threshold effect of disease onset is illustrated. Varying levels of mutant and wild-type mitochondrial DNA (mtDNA) within a mitochondrion are shown. The dashed line represents the threshold at which the accumulation of mutant mtDNA leads to the onset of mitochondrial disease. (Left) mtDNA elimination strategy using mtDNA nucleases. Mutant mtDNA-specific nucleases (shown in green) can selectively target and remove only the mutant mtDNA. Selectively elimination of mutant mtDNA results in a shift in the mutant mtDNA levels within heteroplasmic populations as mtDNA copy numbers are restored. As the concentration of mutant mtDNA drops below the pathogenic threshold, cells can regain a normal phenotype. (Right) mtDNA base editing strategy using mtDNA base editors. mtDNA base editors (shown in green) bind specifically the target DNA and deaminate cytosine (C) or adenine (A) to uracil (U) or hypoxanthine (I), which is further transformed into thymine (T) or guanine (G) during mtDNA replication. MtDNA base editors can be used to create disease models by introducing pathogenic point mutations. Additionally, they can be employed to correct pre-existing pathogenic point mutations.
  • CRISPR base editor-based targeted random mutagenesis (BE-TRM) toolbox for directed evolution

    Schematics of base editor-based targeted random mutagenesis (BE-TRM) tools, their design and hypermutation mechanisms. (A) Representative architectures of BE-TRM tools, including cytosine (CBE), adenine (ABE), glycosylase (CGBE/CABE), dual BE (DuBE), and BE-polymerase fusion are shown, along with their major deaminase variants. (B) CBE consists of Cas nickase (for example, nCas9) fused to cytidine deaminase and the uracil glycosylase inhibitor domain (UGI). It binds to a target DNA sequence and hydrolytically deaminates cytosine to uracil (C-to-U), ultimately resulting in a C-to-T substitution. (C) ABE is created by fusing nCas9 with an evolved adenine deaminase (TadA*). The TadA* enzyme deaminates deoxyadenosine to deoxyinosine (A-to-I), guiding DNA repair through the nicked strand, and finally producing A-to-G editing. (D) CGBE consists of nCas9, cytidine deaminase, and DNA repair proteins such as uracil DNA N-glycosylase (UNG) or XRCC, which facilitate abasic site formation at the deaminated C. This leads to C-to-G (in humans) or C-to-A editing (in bacteria). (E) DuBE combines the components of CBE and ABE to perform simultaneous C-to-T and A-to-G editing. (F) The BE-polymerase fusion toolset is designed by fusing cytidine or TadA* variant to T7 RNA polymerase (T7RNAP). It mutates the gene located between the T7 promoter and T7 terminator through multiple rounds, generating targeted hypermutation.
  • Harnessing CRISPR-Cas adaptation for RNA recording and beyond

    Overview of the mechanism and classification of CRISPR-Cas systems. (A) Schematic of the CRISPR-Cas adaptive immunity. During the adaptation stage, foreign DNA (gray helical lines) or RNA (pink lines) can be captured and integrated into CRISPR array, by Cas1-Cas2 and (Cas6-)RT-Cas1-Cas2 complexes, respectively. Acquired nucleic acids are converted to new spacers and recorded in a leader-proximal order, creating immunological memories. In the expression stage, spacers in CRISPR array are transcribed to pre-crRNA, and processed into crRNAs (crRNA biogenesis). The effector RNP complex are assembled crRNAs with expressed effector Cas proteins. At the final interference stage, effector complexes target against revisiting foreign (viral) DNAs and their transcripts through sequence-specific cleavage complementary to the sequence of crRNA. The image is adopted and modified from Lee et al. Trends in Biochemical Sciences, 2022 (8). (B) Classification and gene structure of CRISPR-Cas systems. In adaptation associated cas genes, there are well conserved genes, Cas1 and Cas2. Some accessory genes exist like Cas4 in type I, II and V, or reverse transcriptase (RT) in type III and VI, or Csn2 in type II. The classification of each type primarily based on effector genes. Class 1 has multiple interfering and crRNA biogenesis genes. Meanwhile, Class 2 has single effector genes, e.g. Cas9, Cas12 or Cas13. The signature proteins in each type are represented with red outline. Target nucleic acids and the existing collateral damage effect are indicated below.

BMB Reports 2024; 57(2): 71~123
Contributed Mini Review
Research progress on hydrogel-based drug therapy in melanoma immunotherapy
Wei He, Yanqin Zhang, Yi Qu, Mengmeng Liu, Guodong Li, Luxiang Pan, Xinyao Xu, Gege Shi, Qiang Hao, Fen Liu & Yuan Gao
BMB Reports 2024; 57(2): 71-78  https://doi.org/10.5483/BMBRep.2023-0160
Phenotypic characterization of pre-harvest sprouting resistance mutants generated by the CRISPR/Cas9-geminiviral replicon system in rice
Jong Hee Kim , Jihyeon Yu , Jin Young Kim , Yong Jin Park , Sangsu Bae , Kwon Kyoo Kang & Yu Jin Jung
BMB Reports 2024; 57(2): 79-85  https://doi.org/10.5483/BMBRep.2023-0210
PDAT1 genome editing reduces hydroxy fatty acid production in transgenic Arabidopsis
Mid-Eum Park & Hyun Uk Kim
BMB Reports 2024; 57(2): 86-91  https://doi.org/10.5483/BMBRep.2023-0039
Glucosamine increases macrophage lipid accumulation by regulating the mammalian target of rapamycin signaling pathway
Sang-Min Kim, Dong Yeol Kim, Jiwon Park, Young-Ah Moon & Inn-Oc Han
BMB Reports 2024; 57(2): 92-97  https://doi.org/10.5483/BMBRep.2023-0158
Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair
Yuna Kim, Baeki E. Kang, Karim Gariani , Joanna Gariani , Junguee Lee , Hyun-Jin Kim , Chang-Woo Lee , Kristina Schoonjans , Johan Auwerx & Dongryeol Ryu
BMB Reports 2024; 57(2): 98-103  https://doi.org/10.5483/BMBRep.2023-0187
Gefitinib induces anoikis in cervical cancer cells
Byung Chul Jung , Sung-Hun Woo , Sung Hoon Kim & Yoon Suk Kim
BMB Reports 2024; 57(2): 104-109  https://doi.org/10.5483/BMBRep.2023-0225
Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer
Hyeran Shim, Kiwon Jang , Yeong Hak Bang , Hoang Bao Khanh Chu , Jisun Kang , Jin-Young Lee , Sheehyun Cho , Hong Seok Lee , Jongbum Jeon , Taeyeon Hwang , Soobok Joe , Jinyeong Lim , Ji-Hye Choi , Eun Hye Joo , Kyunghee Park , Ji Hwan Moon , Kyung Yeon Han , Yourae Hong , Woo Yong Lee , Hee Cheol Kim , Seong Hyeon Yun , Yong Beom Cho , Yoon Ah Park , Jung Wook Huh , Jung Kyong Shin , Dae Hee Pyo , Hyekyung Hong , Hae-Ock Lee, Woong-Yang Park , Jin Ok Yang & Young-Joon Kim
BMB Reports 2024; 57(2): 110-115  https://doi.org/10.5483/BMBRep.2023-0093
Therapeutic potential of BMSC-conditioned medium in an in vitro model of renal fibrosis using the RPTEC/TERT1 cell line
Yunji Kim, Dayeon Kang, Ga-eun Choi , Sang Dae Kim , Sun-ja Yang , Hyosang Kim , Dalsan You , Choung Soo Kim & Nayoung Suh
BMB Reports 2024; 57(2): 116-121  https://doi.org/10.5483/BMBRep.2023-0239
Erratum to: circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis
Kaiyun Qin, Fenghua Zhang, Hongxia Wang , Na Wang , Hongbing Qiu , Xinzhuan Jia, Shan Gong & Zhengmao Zhang
BMB Reports 2024; 57(2): 122-122  
Retraction: Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/β-catenin signaling pathway
Zhe Shi , Liyuan Zhou , Yan Zhou , Xiaoyan Jia , Xiangjun Yu , Xiaohong An & Yanzhen Han
BMB Reports 2024; 57(2): 123-123  


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February 2024
Volume 57
Issue 2

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