Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Yoon Suk Kim
{"title":"Gefitinib induces anoikis in cervical cancer cells.","authors":"Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Yoon Suk Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Gefitinib exerts anticancer effects on various types of cancer, such as lung, ovarian, breast, and colon cancers. However, the therapeutic effects of gefitinib on cervical cancer and the underlying mechanisms remain unclear. Thus, this study aimed to explore whether gefitinib can be used to treat cervical cancer and elucidate the underlying mechanisms. Results showed that gefitinib induced a caspase-dependent apoptosis of HeLa cells, which consequently became round and detached from the surface of the culture plate. Gefitinib induced the reorganization of actin cytoskeleton and downregulated the expression of p-FAK, integrin β1 and E-cadherin, which are important in cell-extracellular matrix adhesion and cell-cell interaction, respectively. Moreover, gefitinib hindered cell reattachment and spreading and suppressed interactions between detached cells in suspension, leading to poly (ADP-ribose) polymerase cleavage, a hallmark of apoptosis. It also induced detachment-induced apoptosis (anoikis) in C33A cells, another cervical cancer cell line. Taken together, these results suggest that gefitinib triggers anoikis in cervical cancer cells. Our findings may serve as a basis for broadening the range of anticancer drugs used to treat cervical cancer. [BMB Reports 2024; 57(2): 104-109].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"104-109"},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10910092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-04DOI: 10.5483/bmbrep.2023-0221
Chul-Sung Park, Omer Habib, Younsu Lee, J. Hur
{"title":"Applications of CRISPR technologies to the development of gene and cell therapy.","authors":"Chul-Sung Park, Omer Habib, Younsu Lee, J. Hur","doi":"10.5483/bmbrep.2023-0221","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0221","url":null,"abstract":"Advancements in gene and cell therapy have resulted in novel therapeutics for diseases previously considered incurable or challenging to treat. Among the various contributing technologies, genome editing stands out as one of the most crucial for the progress in gene and cell therapy. The discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the subsequent evolution of genetic engineering technology have markedly expanded the field of target-specific gene editing. Originally studied in the immune systems of bacteria and archaea, the CRISPR system has demonstrated wide applicability to effective genome editing of various biological systems including human cells. The development of CRISPR-based base editing has enabled directional cytosine-tothymine and adenine-to-guanine substitutions of select DNA bases at the target locus. Subsequent advances in prime editing further elevated the flexibility of the edit multiple consecutive bases to desired sequences. The recent CRISPR technologies also have been actively utilized for the development of in vivo and ex vivo gene and cell therapies. We anticipate that the medical applications of CRISPR will rapidly progress to provide unprecedented possibilities to develop novel therapeutics towards various diseases.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":"33 17","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-04DOI: 10.5483/bmbrep.2023-0248
Ju-Chan Park, Sangsu Bae
{"title":"Current status of genome editing technologies: special issue of BMB Reports in 2024.","authors":"Ju-Chan Park, Sangsu Bae","doi":"10.5483/bmbrep.2023-0248","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0248","url":null,"abstract":"Since the identification of DNA as a genetic material, manipulating DNA in various organisms has been a long standing dream of humanity. In pursuit of this objective, technologies to edit genome have been extensively developed over the recent decades. The emergence of zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems enabled site-specific DNA cleavage in a programmable manner. Furthermore, the advent of base editors (BEs) and prime editors (PEs) has enabled base conversion and insertion/deletion with a high accuracy. In addition to the editing of genomic DNA in the nucleus, attempts to manipulate circular DNAs in organelle are currently ongoing. These technologies are bringing major progress in diverse fields including the engineering of cells, livestock, and plants as well as therapeutic gene correction in humans. In this special issue, we aim to cover the recent advances in genome editing technology and its applications in therapeutics, breed improvement in plants and livestock, RNA recording, and protein evolution.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":"11 12","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BMB ReportsPub Date : 2024-01-04DOI: 10.5483/bmbrep.2023-0224
Kayeong Lim
{"title":"Mitochondrial genome editing: strategies, challenges, and applications.","authors":"Kayeong Lim","doi":"10.5483/bmbrep.2023-0224","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0224","url":null,"abstract":"Mitochondrial DNA (mtDNA), a multicopy genome found in mitochondria, is crucial for oxidative phosphorylation. Mutations in mtDNA can lead to severe mitochondrial dysfunction in tissues and organs with high energy demand. MtDNA mutations are closely associated with mitochondrial and age-related disease. To better understand the functional role of mtDNA and work toward developing therapeutics, it is essential to advance technology that is capable of manipulating the mitochondrial genome. This review discusses ongoing efforts in mitochondrial genome editing with mtDNA nucleases and base editors, including the tools, delivery strategies, and applications. Future advances in mitochondrial genome editing to address challenges regarding their efficiency and specificity can achieve the promise of therapeutic genome editing.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":"22 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondrial genome editing: strategies, challenges, and applications.","authors":"Kayeong Lim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mitochondrial DNA (mtDNA), a multicopy genome found in mitochondria, is crucial for oxidative phosphorylation. Mutations in mtDNA can lead to severe mitochondrial dysfunction in tissues and organs with high energy demand. MtDNA mutations are closely associated with mitochondrial and age-related disease. To better understand the functional role of mtDNA and work toward developing therapeutics, it is essential to advance technology that is capable of manipulating the mitochondrial genome. This review discusses ongoing efforts in mitochondrial genome editing with mtDNA nucleases and base editors, including the tools, delivery strategies, and applications. Future advances in mitochondrial genome editing to address challenges regarding their efficiency and specificity can achieve the promise of therapeutic genome editing. [BMB Reports 2024; 57(1): 19-29].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"19-29"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent advances in genome engineering by CRISPR technology.","authors":"Youngsik Lee, Yeounsun Oh, Seung Hwan Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Due to the development of CRISPR technology, the era of effective editing of target genes has arrived. However, the offtarget problem that occurs when recognizing target DNA due to the inherent nature of CRISPR components remains the biggest task to be overcome in the future. In this review, the principle of inducing such unintended off-target editing is analyzed from the structural aspect of CRISPR, and the methodology that has been developed to reduce off-target editing until now is summarized. [BMB Reports 2024; 57(1): 12-18].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"12-18"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current status of genome editing technologies: special issue of BMB Reports in 2024.","authors":"Ju-Chan Park, Sangsu Bae","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Since the identification of DNA as a genetic material, manipulating DNA in various organisms has been a long standing dream of humanity. In pursuit of this objective, technologies to edit genome have been extensively developed over the recent decades. The emergence of zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems enabled site-specific DNA cleavage in a programmable manner. Furthermore, the advent of base editors (BEs) and prime editors (PEs) has enabled base conversion and insertion/deletion with a high accuracy. In addition to the editing of genomic DNA in the nucleus, attempts to manipulate circular DNAs in organelle are currently ongoing. These technologies are bringing major progress in diverse fields including the engineering of cells, livestock, and plants as well as therapeutic gene correction in humans. In this special issue, we aim to cover the recent advances in genome editing technology and its applications in therapeutics, breed improvement in plants and livestock, RNA recording, and protein evolution. [BMB Reports 2024; 57(1): 1].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rahul Mahadev Shelake, Dibyajyoti Pramanik, Jae-Yean Kim
{"title":"CRISPR base editor-based targeted random mutagenesis (BE-TRM) toolbox for directed evolution.","authors":"Rahul Mahadev Shelake, Dibyajyoti Pramanik, Jae-Yean Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Directed evolution (DE) of desired locus by targeted random mutagenesis (TRM) tools is a powerful approach for generating genetic variations with novel or improved functions, particularly in complex genomes. TRM-based DE involves developing a mutant library of targeted DNA sequences and screening the variants for the desired properties. However, DE methods have for a long time been confined to bacteria and yeasts. Lately, CRISPR/Cas and DNA deaminase-based tools that circumvent enduring barriers such as longer life cycle, small library sizes, and low mutation rates have been developed to facilitate DE in native genetic environments of multicellular organisms. Notably, deaminase-based base editing-TRM (BE-TRM) tools have greatly expanded the scope and efficiency of DE schemes by enabling base substitutions and randomization of targeted DNA sequences. BE-TRM tools provide a robust platform for the continuous molecular evolution of desired proteins, metabolic pathway engineering, creation of a mutant library of desired locus to evolve novel functions, and other applications, such as predicting mutants conferring antibiotic resistance. This review provides timely updates on the recent advances in BE-TRM tools for DE, their applications in biology, and future directions for further improvements. [BMB Reports 2024; 57(1): 30-39].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"30-39"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dong-Hyeok Kwon, Gyeong-Min Gim, Soo-Young Yum, Goo Jang
{"title":"Current status and future of gene engineering in livestock.","authors":"Dong-Hyeok Kwon, Gyeong-Min Gim, Soo-Young Yum, Goo Jang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The application of gene engineering in livestock is necessary for various reasons, such as increasing productivity and producing disease resistance and biomedicine models. Overall, gene engineering provides benefits to the agricultural and research aspects, and humans. In particular, productivity can be increased by producing livestock with enhanced growth and improved feed conversion efficiency. In addition, the application of the disease resistance models prevents the spread of infectious diseases, which reduces the need for treatment, such as the use of antibiotics; consequently, it promotes the overall health of the herd and reduces unexpected economic losses. The application of biomedicine could be a valuable tool for understanding specific livestock diseases and improving human welfare through the development and testing of new vaccines, research on human physiology, such as human metabolism or immune response, and research and development of xenotransplantation models. Gene engineering technology has been evolving, from random, time-consuming, and laborious methods to specific, time-saving, convenient, and stable methods. This paper reviews the overall trend of genetic engineering technologies development and their application for efficient production of genetically engineered livestock, and provides examples of technologies approved by the United States (US) Food and Drug Administration (FDA) for application in humans. [BMB Reports 2024; 57(1): 50-59].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"50-59"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A Reum Han, Ha Rim Shin, Jiyeon Kwon, Soo Been Lee, Sang Eun Lee, Eun-Young Kim, Jiyeon Kweon, Eun-Ju Chang, Yongsub Kim, Seong Who Kim
{"title":"Highly efficient genome editing via CRISPR-Cas9 ribonucleoprotein (RNP) delivery in mesenchymal stem cells.","authors":"A Reum Han, Ha Rim Shin, Jiyeon Kwon, Soo Been Lee, Sang Eun Lee, Eun-Young Kim, Jiyeon Kweon, Eun-Ju Chang, Yongsub Kim, Seong Who Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The CRISPR-Cas9 system has significantly advanced regenerative medicine research by enabling genome editing in stem cells. Due to their desirable properties, mesenchymal stem cells (MSCs) have recently emerged as highly promising therapeutic agents, which properties include differentiation ability and cytokine production. While CRISPR-Cas9 technology is applied to develop MSC-based therapeutics, MSCs exhibit inefficient genome editing, and susceptibility to plasmid DNA. In this study, we compared and optimized plasmid DNA and RNP approaches for efficient genome engineering in MSCs. The RNP-mediated approach enabled genome editing with high indel frequency and low cytotoxicity in MSCs. By utilizing Cas9 RNPs, we successfully generated B2M-knockout MSCs, which reduced T-cell differentiation, and improved MSC survival. Furthermore, this approach enhanced the immunomodulatory effect of IFN-r priming. These findings indicate that the RNP-mediated engineering of MSC genomes can achieve high efficiency, and engineered MSCs offer potential as a promising therapeutic strategy. [BMB Reports 2024; 57(1): 60-65].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"60-65"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}