Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Yoon Suk Kim
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].
{"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":null,"pages":null},"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}
Pub Date : 2024-01-31DOI: 10.5483/BMBRep.2023-0239
Yunji Kim, D. Kang, Ga-Eun Choi, Sang Dae Kim, Sun-Ja Yang, Hyosang Kim, D. You, Choung Soo Kim, N. Suh
We investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell-conditioned medium (BMSC-CM) on immortalized renal proximal tubule epithelial cells (RPTEC/TERT1) in a fibrotic environment. To replicate the increased stiffness characteristic of kidneys in chronic kidney disease, we utilized polyacrylamide gel platforms. A stiff matrix was shown to increase α-smooth muscle actin (α-SMA) levels, indicating fibrogenic activation in RPTEC/TERT1 cells. Interestingly, treatment with BMSC-CM resulted in significant reductions in the levels of fibrotic markers (α-SMA and vimentin) and increases in the levels of the epithelial marker E-cadherin and aquaporin 7, particularly under stiff conditions. Furthermore, BMSC-CM modified microRNA (miRNA) expression and reduced oxidative stress levels in these cells. Our findings suggest that BMSC-CM can modulate cellular morphology, miRNA expression, and oxidative stress in RPTEC/TERT1 cells, highlighting its therapeutic potential in fibrotic kidney disease.
{"title":"Therapeutic potential of BMSC-conditioned medium in an in vitro model of renal fibrosis using the RPTEC/TERT1 cell line","authors":"Yunji Kim, D. Kang, Ga-Eun Choi, Sang Dae Kim, Sun-Ja Yang, Hyosang Kim, D. You, Choung Soo Kim, N. Suh","doi":"10.5483/BMBRep.2023-0239","DOIUrl":"https://doi.org/10.5483/BMBRep.2023-0239","url":null,"abstract":"We investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell-conditioned medium (BMSC-CM) on immortalized renal proximal tubule epithelial cells (RPTEC/TERT1) in a fibrotic environment. To replicate the increased stiffness characteristic of kidneys in chronic kidney disease, we utilized polyacrylamide gel platforms. A stiff matrix was shown to increase α-smooth muscle actin (α-SMA) levels, indicating fibrogenic activation in RPTEC/TERT1 cells. Interestingly, treatment with BMSC-CM resulted in significant reductions in the levels of fibrotic markers (α-SMA and vimentin) and increases in the levels of the epithelial marker E-cadherin and aquaporin 7, particularly under stiff conditions. Furthermore, BMSC-CM modified microRNA (miRNA) expression and reduced oxidative stress levels in these cells. Our findings suggest that BMSC-CM can modulate cellular morphology, miRNA expression, and oxidative stress in RPTEC/TERT1 cells, highlighting its therapeutic potential in fibrotic kidney disease.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140474970","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}
Pub Date : 2024-01-26DOI: 10.5483/bmbrep.2023-0225
Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Y. Kim
{"title":"Gefitinib induces anoikis in cervical cancer cells","authors":"Byung Chul Jung, Sung-Hun Woo, Sung Hoon Kim, Y. Kim","doi":"10.5483/bmbrep.2023-0225","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0225","url":null,"abstract":"","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139593506","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}
Pub Date : 2024-01-18DOI: 10.5483/bmbrep.2023-0210
Jong Hee Kim, Jihyeon Yu, Jin Young Kim, Yong Jin Park, Sangsu Bae, Kwon Kyoo Kang, Yu-Jin Jung
{"title":"Phenotypic characterization of pre-harvest sprouting resistance mutants generated by the CRISPR/Cas9-geminiviral replicon system in rice","authors":"Jong Hee Kim, Jihyeon Yu, Jin Young Kim, Yong Jin Park, Sangsu Bae, Kwon Kyoo Kang, Yu-Jin Jung","doi":"10.5483/bmbrep.2023-0210","DOIUrl":"https://doi.org/10.5483/bmbrep.2023-0210","url":null,"abstract":"","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139526584","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}
Pub Date : 2024-01-04DOI: 10.5483/bmbrep.2023-0221
Chul-Sung Park, Omer Habib, Younsu Lee, J. Hur
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.
基因和细胞疗法的进步为以前被认为无法治愈或难以治疗的疾病带来了新的疗法。在各种促进技术中，基因组编辑技术是基因和细胞疗法取得进展的最关键技术之一。CRISPR（Clustered Regularly Interspaced Short Palindromic Repeats）的发现以及随后基因工程技术的发展，极大地拓展了靶向基因编辑领域。CRISPR 系统最初是在细菌和古细菌的免疫系统中进行研究的，现已广泛应用于包括人类细胞在内的各种生物系统的有效基因组编辑。基于 CRISPR 的碱基编辑技术的发展实现了目标基因座上特定 DNA 碱基的胞嘧啶-胸腺嘧啶和腺嘌呤-鸟嘌呤定向替换。随后的素材编辑技术进一步提高了将多个连续碱基编辑为所需序列的灵活性。最近，CRISPR 技术还被积极用于体内和体外基因和细胞疗法的开发。我们预计，CRISPR 的医学应用将迅速发展，为开发针对各种疾病的新型疗法提供前所未有的可能性。
{"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":null,"pages":null},"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}
Pub Date : 2024-01-04DOI: 10.5483/BMBRep.2023-0187
Y. Kim, Baeki E Kang, Karim Gariani, Joanna Gariani, Junguee Lee, Hyun-Jin Kim, Chang-Woo Lee, Kristina Schoonjans, Johan Auwerx, Dongryeol Ryu
The mammalian sirtuin family (SIRT1–SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.
哺乳动物 sirtuin 家族（SIRT1-SIRT7）在基因毒性胁迫下调节和维持基因组稳定性方面发挥了多种生物学作用。SIRT7是研究最少的sirtuin之一，已被证明是DNA损伤应答（DDR）的关键因素。然而，一些相互矛盾的结果认为 Sirt7 是促进癌细胞转化的致癌因子。为了解决这一矛盾，我们研究了SIRT7在肝癌（HCC）DNA损伤调控中的特性，发现肝脏Sirt7的缺失会加速HCC的进展。具体来说，在注射了二乙基亚硝胺（DEN）的Sirt7缺失肝脏中，肝肿瘤菌落的数量、大小和体积都明显增加。此外，与对照组不同，肝脏Sirt7缺失时，HCC进展标志物和促炎细胞因子的水平显著升高。在染色质中，SIRT7 通过抑制 DNA 损伤下 γH2AX 的诱导而稳定并定位在损伤位点上。总之，我们的研究结果表明，SIRT7是DNA损伤修复的关键因子，肝脏缺失Sirt7会促进基因组的不稳定性并加速HCC的发展，这与早期关于Sirt7是致癌因子的研究不同。
{"title":"Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair","authors":"Y. Kim, Baeki E Kang, Karim Gariani, Joanna Gariani, Junguee Lee, Hyun-Jin Kim, Chang-Woo Lee, Kristina Schoonjans, Johan Auwerx, Dongryeol Ryu","doi":"10.5483/BMBRep.2023-0187","DOIUrl":"https://doi.org/10.5483/BMBRep.2023-0187","url":null,"abstract":"The mammalian sirtuin family (SIRT1–SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140514107","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}
Pub Date : 2024-01-04DOI: 10.5483/bmbrep.2023-0248
Ju-Chan Park, Sangsu Bae
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.
自从 DNA 被确认为遗传物质以来，操纵各种生物的 DNA 一直是人类的夙愿。为了实现这一目标，近几十年来基因组编辑技术得到了广泛的发展。锌指核酸酶（ZFN）、转录激活剂样效应核酸酶（TALEN）、簇状规则间隔短回文重复序列（CRISPR）和CRISPR相关（Cas）系统的出现，实现了以可编程的方式定点切割DNA。此外，碱基编辑器（BE）和质粒编辑器（PE）的出现也实现了高精度的碱基转换和插入/删除。除了编辑细胞核中的基因组 DNA 外，目前还在尝试操纵细胞器中的环状 DNA。这些技术在多个领域都取得了重大进展，包括细胞、牲畜和植物工程以及人类治疗性基因矫正。本特刊旨在介绍基因组编辑技术的最新进展及其在治疗、植物和家畜品种改良、RNA记录和蛋白质进化方面的应用。
{"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":null,"pages":null},"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}
Pub Date : 2024-01-04DOI: 10.5483/bmbrep.2023-0224
Kayeong Lim
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.
{"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":null,"pages":null},"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}
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].
{"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":null,"pages":null},"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}
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].
{"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":null,"pages":null},"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}
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