Review
Genetics & Heredity
Mehmet Cengiz Baloglu, Yasemin Celik Altunoglu, Pinar Baloglu, Ali Burak Yildiz, Nil Turkolmez, Yelda Ozden ciftci
Summary: Legumes are rich in protein and phytochemicals, and their genetic traits have been improved using genome editing technologies. However, governmental regulatory restrictions present a concern.
FRONTIERS IN GENETICS
(2022)
Review
Physiology
Amina Saleem, Muhammad Khawar Abbas, Yongming Wang, Feng Lan
Summary: Research has shown that human pluripotent stem cell-derived cardiomyocytes have significantly advanced the study of cardiovascular disease mechanisms. In recent years, advancements in genome editing techniques have greatly improved the efficiency of cell-based mechanism study and therapy for cardiac diseases.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Tae Hyeong Kim, Seong-Wook Lee
Summary: Viral infections pose a serious threat to human health and require the development of vaccines and antiviral therapeutic agents. Genome editing technology enables precise modification of genomic sequences and has expanded its applicability in developing therapeutics for viral diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biotechnology & Applied Microbiology
Dongwon Baek, Hyun Jin Chun, Min Chul Kim
Summary: Soybean is a major economic crop used for food, feed, and biofuel. Traditional and molecular breeding methods have improved its quality and yield, but genetic limitations and social issues have hindered the breeding of new varieties. Genome editing technologies, such as ZFN, TALEN, and CRISPR/Cas9, have revolutionized the study of genetic variations and soybean improvement.
PLANT BIOTECHNOLOGY REPORTS
(2022)
Review
Pharmacology & Pharmacy
Amanda Catalina Ramirez-Phillips, Dexi Liu
Summary: Advancements in understanding human genetics have fueled interest in therapeutic genome editing using engineered nucleases, with CRISPR/Cas9 emerging as a cost-effective and efficient system. Clinical applications of CRISPR/Cas9 include treatments for genetic diseases and cancer, highlighting its potential for targeted genetic modifications and viral infection eradication. Future progress in therapeutic genome editing will rely on improved delivery methods and repair efficiency for site-specific gene modification.
Review
Medicine, General & Internal
Bogdan Doroftei, Ovidiu-Dumitru Ilie, Maria Puiu, Alin Ciobica, Ciprian Ilea
Summary: Infertility is a controversial topic with a genetic basis being recognized as a new perspective for understanding the disease. Research indicates that some genes are dispensable for fertility without affecting host homeostasis, while loss of function in certain genes can lead to moderate to severe phenotypic changes.
Review
Biochemistry & Molecular Biology
Michelle C. E. Mak, Rijan Gurung, Roger S. Y. Foo
Summary: Cardiovascular diseases, especially coronary artery disease (CAD), are the leading cause of death globally. Atherosclerosis is a major factor in CAD, and genome editing technologies can be used to establish models of atherosclerosis and have therapeutic roles in treating atherosclerosis and the clinical implications of CAD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Fernando Gomez-Garcia, Raquel Martinez-Pulleiro, Noa Carrera, Catarina Allegue, Miguel A. Garcia-Gonzalez
Summary: This study discusses the genetic causes and phenotypic effects of genetic kidney diseases (GKDs) and describes and compares the application of site-specific nuclease systems (such as ZFNs, TALENs, and CRISPR-Cas9). It demonstrates that these systems can be used to edit the genes causing GKDs and generate models that reflect the genetic abnormalities, thus shedding light on many unknown aspects in the field of GKDs.
Review
Genetics & Heredity
Roya Ramezankhani, Neda Minaei, Mahnaz Haddadi, Shukoofeh Torabi, Mahdi Hesaraki, Hamed Mirzaei, Massoud Vosough, Catherine M. Verfaillie
Summary: Gene correction is a promising strategy to treat genetic diseases, with genome editing tools like CRISPR/Cas9 considered novel technologies capable of correcting genetic aberrations. While the increasing number of clinical trials show encouraging outcomes, challenges remain regarding safety and targeted delivery.
Review
Medicine, Research & Experimental
Saikat Mitra, Joyatry Sarker, Anik Mojumder, Tasmim Bintae Shibbir, Rajib Das, Talha Bin Emran, Trina Ekawati Tallei, Firzan Nainu, Asma M. Alshahrani, Kumarappan Chidambaram, Jesus Simal-Gandara
Summary: Cancer is a common and deadly disease worldwide, with metastasis being the main cause. Gene editing techniques can help discover new drug targets and study the molecular mechanisms of cancer. Among these techniques, CRISPR/Cas9 stands out for its high efficiency and precision. Its applications in cancer research contribute to improving cancer treatment and overcoming current challenges.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biotechnology & Applied Microbiology
Congting Guo, Xiaoteng Ma, Fei Gao, Yuxuan Guo
Summary: Gene editing involves precise changes to specific nucleic acid sequences. The CRISPR/Cas9 system has revolutionized gene editing, making it efficient, convenient, and programmable. However, off-target effects remain a major concern, leading to unexpected alterations in the genome. Various methods have been developed to detect and mitigate these off-target effects, advancing the precision of CRISPR/Cas9 derivatives. This review summarizes these technological advancements and discusses the challenges in managing off-target effects for future gene therapy.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Review
Biology
Ilnaz Rahimmanesh, Maryam Boshtam, Shirin Kouhpayeh, Hossein Khanahmad, Arezou Dabiri, Shahrzad Ahangarzadeh, Yasaman Esmaeili, Elham Bidram, Golnaz Vaseghi, Shaghayegh Haghjooy Javanmard, Laleh Shariati, Ali Zarrabi, Rajender S. Varma
Summary: Beta-thalassemia is a heterogeneous blood disorder that can be treated using gene editing tools, but there are still challenges to address, such as off-target effects and immunotoxicity.
Review
Biochemistry & Molecular Biology
Jochen Dobner, Haribaskar Ramachandran, Andrea Rossi
Summary: Genome editing techniques offer the opportunity for precise treatment of human diseases by manipulating the genomes. Recent breakthroughs have been made and clinical trials employing genome editing-based medicine are underway. However, ethical and regulatory guidelines need to be developed and potential risks and future development of this technology need to be further studied.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2022)
Review
Biochemistry & Molecular Biology
Anshu Sahu, Rita Verma, Uma Gupta, Shashi Kashyap, Indraneel Sanyal
Summary: Anti-nutrients, such as phytic acid, can inactivate nutrients and impair their metabolism. Removing these substances from cereal grains can enhance the availability of nutrients. Different strategies have been used to reduce phytic acid content, including using genetic engineering tools like TALEN, ZFN, CRISPR/Cas9, and RNAi to target genes involved in its biosynthesis.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Zhixin Lei, Haowei Meng, Yuan Zhuang, Qingguo Zhu, Chengqi Yi
Summary: This article outlines the off-target effects observed for various genome editing tools and discusses the methods for detecting and evaluating off-target editing, along with their advantages and limitations. Additionally, it summarizes current RNA editing tools for RNA therapy and medicine that can potentially serve as alternative approaches to genome editing tools in research and clinical applications.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Daesik Kim, Beum-Chang Kang, Jin-Soo Kim
Summary: Digenome-seq is a cell-free method for identifying genome-wide off-target sites of programmable nucleases and deaminases, which is more sensitive and comprehensive than cell-based methods and does not involve DNA end enrichment through PCR amplification. The process takes about several weeks, including purification and preparation of RNPs, digestion of genomic DNA, and bioinformatic analysis after WGS.
Article
Biochemistry & Molecular Biology
Ha Rim Shin, Ji-Eun See, Jiyeon Kweon, Heon Seok Kim, Gi-Jun Sung, Sojung Park, An-Hee Jang, Gayoung Jang, Kyung-Chul Choi, Inki Kim, Jin-Soo Kim, Yongsub Kim
Summary: CRISPR-based base editors are widely used for nucleotide substitutions without causing DNA breaks. Efforts are being made to improve the efficiency of both cytosine and adenine base editors. A study has identified histone deacetylase inhibitors, particularly romidepsin, as a potential option to enhance base editing efficiency.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Hyunji Lee, Seonghyun Lee, Gayoung Baek, Annie Kim, Beum-Chang Kang, Huiyun Seo, Jin-Soo Kim
Summary: This study demonstrates highly efficient mitochondrial DNA editing using DdCBEs in mouse embryos, creating mitochondrial disease models and showing the potential for treating mitochondrial disorders. The authors show the use of split DddA-derived base editors fused to TALEs in mouse embryos with germline transmission.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Pin Lyu, Zuyan Lu, Sung-Ik Cho, Manish Yadav, Kyung Whan Yoo, Anthony Atala, Jin-Soo Kim, Baisong Lu
Summary: This study developed a delivery method to reduce RNA off-target activities of ABEs using electroporation or lentiviral capsids. These methods enabled efficient guided base editing with stable detectable RNA off-target activities. This approach makes ABE closer to possible therapeutic applications.
Article
Multidisciplinary Sciences
Terence Y. W. Lam, Ngan Nguyen, Hong Yong Peh, Mahalakshmi Shanmugasundaram, Ritu Chandna, Jong Huat Tee, Chee Bing Ong, Md. Zakir Hossain, Shruthi Venugopal, Tianyi Zhang, Simin Xu, Tao Qiu, Wan Ting Kong, Svetoslav Chakarov, Supriya Srivastava, Wupeng Liao, Jin-Soo Kim, Ming Teh, Florent Ginhoux, W. S. Fred, Ruowen Ge
Summary: This study reveals the importance of alveolar macrophages (AMs) in maintaining lung homeostasis and their role in chronic obstructive pulmonary disease (COPD). The absence of IST1 protein leads to increased AM numbers and altered functions, resulting in lung inflammation and COPD-like symptoms. The study also identifies csGRP78high AMs as the primary targets of IST1-mediated apoptosis. Intratracheal delivery of recombinant IST1 shows potential as a therapeutic strategy for COPD by targeting csGRP78.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Kayeong Lim, Sung-Ik Cho, Jin-Soo Kim
Summary: The researchers propose a novel base editing platform that enables targeted C-to-T base conversions in human cells without inducing insertions and deletions. The platform, called zinc finger deaminases (ZFDs), consists of custom-designed zinc-finger DNA-binding proteins, the split interbacterial toxin deaminase DddA(tox), and a uracil glycosylase inhibitor (UGI). By assembling plasmids encoding ZFDs using publicly available zinc finger resources, base editing can be achieved at high frequencies in both nuclear DNA and mtDNA. Unlike CRISPR-derived base editors, ZFDs do not cleave DNA and therefore do not produce unwanted indels at target sites. Additionally, recombinant ZFD proteins expressed in and purified from E. coli can penetrate cultured human cells spontaneously, demonstrating the proof-of-principle of gene-free gene therapy.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Sung-Ik Cho, Seonghyun Lee, Young Geun Mok, Kayeong Lim, Jaesuk Lee, Ji Min Lee, Eugene Chung, Jin-Soo Kim
Summary: Mitochondrial DNA editing is crucial for modeling mitochondrial genetic disorders and potential future treatments. This study presents a new editing enzyme called TALEDs, which efficiently induce A-to-G editing in human mitochondria.
Article
Biochemistry & Molecular Biology
Hyun Ju Oh, Eugene Chung, Jaehwan Kim, Min Jung Kim, Geon A. Kim, Seok Hee Lee, Kihae Ra, Kidong Eom, Soojin Park, Jong-Hee Chae, Jin-Soo Kim, Byeong Chun Lee
Summary: A dystrophin mutant dog was successfully generated using the CRISPR/Cas9 system and somatic cell nuclear transfer in this study. This model can be used to study human dystrophinopathy and aid in the development of gene therapy drugs for dogs and humans.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Se-Youl Chae, Euihwan Jeong, Seounghun Kang, Yeajee Yim, Jin-Soo Kim, Dal-Hee Min
Summary: Researchers have developed a porous nanoparticle called BALL for efficient delivery of CRISPR/Cas9 endonuclease. The BALL-mediated delivery of Cas9 RNP showed high efficiency in gene knockout both in vitro and in vivo, and successfully treated muscular dystrophy in animal models.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Multidisciplinary Sciences
Daniel Whisenant, Kayeong Lim, Gwladys Revechon, Haidong Yao, Martin O. Bergo, Piotr Machtel, Jin-Soo Kim, Maria Eriksson
Summary: In this study, the authors successfully corrected the mutation in the skin of HGPS mice by transient adenine base editor expression, improving the skin phenotype of HGPS mice. This approach has the potential to be an effective method for future gene-editing therapies.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Young Geun Mok, Ji Min Lee, Eugene Chung, Jaesuk Lee, Kayeong Lim, Sung-Ik Cho, Jin-Soo Kim
Summary: This study presents non-toxic, full-length variants of DddAtox, enabling the use of monomeric DdCBEs for efficient editing of mitochondrial DNA. The monomeric DdCBEs showed different mutation patterns compared to conventional dimeric DdCBEs and allowed base editing at sites with only one TALE protein. Additionally, transfecting mRNA encoding mDdCBEs reduced off-target editing in human mitochondrial DNA.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Seonghyun Lee, Hyunji Lee, Gayoung Baek, Jin-Soo Kim
Summary: Protein engineering has minimized the off-target activity of DddA-derived base editors (DdCBEs), allowing efficient and precise editing of mitochondrial DNA in human cells. This technology may provide a new approach for therapeutic correction of gene mutation diseases.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jaesuk Lee, Kayeong Lim, Annie Kim, Young Geun Mok, Eugene Chung, Sung-Ik Cho, Ji Min Lee, Jin-Soo Kim
Summary: In this study, the authors analyzed the on- and off-target nicks produced by Cas9 nickases and found that nCas9 (H840A) can cleave both strands and cause unwanted DNA double-strand breaks, while nCas9 (D10A) can only cleave one strand. They also found that incorporating additional mutations into nCas9 (H840A) can further inactivate the HNH nuclease domain and reduce the frequency of unwanted indels caused by error-prone repair of double-strand breaks.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Jin-Soo Kim, Jia Chen
Summary: Mitochondria and chloroplasts are organelles that have their own genomes and targeted editing of these organelles' DNA can have therapeutic, agricultural and environmental potential. Recent advancements in protein-only base editors have enabled targeted organellar DNA editing in living cells. This review discusses the programmable deaminases developed for base editing and the precision and efficiency limitations of these tools.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Plant Sciences
Young Geun Mok, Sunghyun Hong, Su-Ji Bae, Sung-Ik Cho, Jin-Soo Kim
Summary: Chloroplast DNA encodes important genes, but current gene editing technologies cannot be used for editing organellar DNA. However, a new CRISPR-free, protein-only base editor can be used for C-to-T mutations in chloroplast DNA. We demonstrate the heritable A-to-G edits in chloroplast DNA, leading to phenotypic changes, by using transcription activator-like effector-linked deaminases.
