Article
Pharmacology & Pharmacy
Yuanyuan Han, Xiaoyu Tan, Tingting Jin, Siqi Zhao, Li Hu, Wei Zhang, Ryo Kurita, Yukio Nakamura, Juan Liu, Di Li, Zhaojun Zhang, Xiangdong Fang, Shengwen Huang
Summary: This study explores the potential use of CRISPR/Cas9 technology to edit the BCL11A gene for the treatment of beta-hemoglobinopathies. Multiplex gene editing was found to increase the expression of gamma-globin without inhibiting erythroid differentiation. Furthermore, the editing efficiency exceeded 50% when optimized. The study suggests the accuracy and effectiveness of this approach.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
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.
Article
Multidisciplinary Sciences
Jiaoyang Liao, Shuanghong Chen, Shenlin Hsiao, Yanhong Jiang, Yang Yang, Yuanjin Zhang, Xin Wang, Yongrong Lai, Daniel E. Bauer, Yuxuan Wu
Summary: Researchers applied adenine base editing technology to the hematopoietic stem cells of beta-thalassemia patients, successfully introducing nucleotide substitutions to enhance fetal hemoglobin expression and correct common mutations. These findings suggest the potential of adenine base editing for the treatment of inherited monogenic blood disorders.
NATURE COMMUNICATIONS
(2023)
Review
Medicine, General & Internal
Anthony Quagliano, Daniel Acevedo, Patrik Hardigan, Samiksha Prasad
Summary: Beta-hemoglobinopathies, including sickle cell disease and beta-thalassemia, are genetic disorders characterized by mutations in the HBB gene. Current treatments involve pharmacological agents to raise levels of fetal hemoglobin, but gene editing technologies like CRISPR/Cas9 offer potential permanent effects. This meta-analysis compared two gene editing targets, BCL11A and HBG1/2, and found that HBG1/2 significantly increased HbF expression compared to BCL11A.
FRONTIERS IN MEDICINE
(2022)
Article
Medicine, Research & Experimental
Lurong Jiang, Jie Long, Yang Yang, Lifang Zhou, Jing Su, Fengming Qin, Wenling Tang, Rui Tao, Qiang Chen, Shaohua Yao
Summary: In this study, a subset of base editors derived from SaCas9 was designed, which increased the editing efficiency and expanded the editing window by changing the insertion position of the deaminase. These base editors also showed reduced non-specific editing.
Article
Multidisciplinary Sciences
Eric N. Olson
Summary: Recent advances in gene editing technologies show potential for correcting devastating monogenic disorders like Duchenne muscular dystrophy by eliminating underlying genetic mutations. However, challenges remain in optimizing gene editing, delivering editing components throughout muscle tissue, and managing possible immune responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Si-Wei Wang, Chao Gao, Yi-Min Zheng, Li Yi, Jia-Cheng Lu, Xiao-Yong Huang, Jia-Bin Cai, Peng-Fei Zhang, Yue-Hong Cui, Ai-Wu Ke
Summary: The CRISPR/Cas9 gene editing technology has made significant progress in oncological research, providing a powerful tool for exploring the mechanism of cancer, establishing tumor models, and studying drug targets.
Article
Chemistry, Multidisciplinary
Fangfang Shen, Ge Zheng, Mekedlawit Setegne, Karin Tenglin, Manizheh Izadi, Henry Xie, Liting Zhai, Stuart H. Orkin, Laura M. K. Dassama
Summary: In this study, we identified a protein ligand selective for BCL11A using yeast surface display of synthetic nanobodies. Fusion of this ligand to a cell-permeant miniature protein and an E3 adaptor creates a degrader that depletes cellular BCL11A, inducing the expression of fetal hemoglobin. This novel strategy provides a means of fetal hemoglobin induction and targeted degradation of previously intractable proteins.
ACS CENTRAL SCIENCE
(2022)
Review
Materials Science, Multidisciplinary
Shao Wei Hu, Tao Ding, Honghai Tang, Huiping Guo, Wenguo Cui, Yilai Shu
Summary: With the advancement of genome editing techniques, gene therapy is increasingly being used for the treatment of various human diseases. Nanomaterials have shown great potential in improving the efficiency and safety of gene editing in gene therapy. This review introduces three gene editing tools, with a particular focus on the development and optimization of the CRISPR system. It also discusses the recent application of nanobiomaterials in gene therapy, along with the prospects and remaining challenges. Lastly, future directions for gene editing tools, nanobiomaterial vectors, and gene therapy are presented.
Article
Medicine, Research & Experimental
Vigneshwaran Venkatesan, Abisha Crystal Christopher, Manuel Rhiel, Manoj Kumar K. Azhagiri, Prathibha Babu, Kaivalya Walavalkar, Bharath Saravanan, Geoffroy Andrieux, Sumathi Rangaraj, Saranya Srinivasan, Karthik Karuppusamy, Annlin Jacob, Abhirup Bagchi, Aswin Anand Pai, Yukio Nakamura, Ryo Kurita, Poonkuzhali Balasubramanian, Rekha Pai, Srujan Kumar Marepally, Kumarasamypet Murugesan Mohankumar, Shaji R. Velayudhan, Melanie Boerries, Dimple Notani, Toni Cathomen, Alok Srivastava, Saravanabhavan Thangavel
Summary: Reactivation of fetal hemoglobin is a common strategy for treating β-hemoglobinopathies. This study identified a specific genetic mutation that can effectively inhibit the production of adult hemoglobin and increase fetal hemoglobin production. Gene editing of patient hematopoietic stem cells resulted in therapeutic levels of fetal hemoglobin and improved the phenotypes of both sickle cell disease and β-thalassemia major.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Genetics & Heredity
Lucia Carmela Cosenza, Cristina Zuccato, Matteo Zurlo, Roberto Gambari, Alessia Finotti
Summary: Gene editing is an effective strategy for correcting genetic mutations in monogenic hereditary diseases, and combining it with HbF induction protocols can achieve de novo production of HbA and an increase in induced HbF.
Article
Multidisciplinary Sciences
Hainan Zhao, Mingyu Yang, Jade Bishop, Yuhan Teng, Yingxue Cao, Brandon D. Beall, Shuanglin Li, Tongxin Liu, Qingxi Fang, Chao Fang, Haoyang Xin, Hans-Wilhelm Nutzmann, Anne Osbourn, Fanli Meng, Jiming Jiang
Summary: This study surveyed the genomic regions in Arabidopsis thaliana and identified a set of putative super-enhancers (SEs) that are associated with topologically associating domains (TADs) and play a role in organ development and tissue identity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Ganna Reint, Zhuokun Li, Kornel Labun, Salla Keskitalo, Inkeri Soppa, Katariina Mamia, Eero Tolo, Monika Szymanska, Leonardo A. Meza-Zepeda, Susanne Lorenz, Artur Cieslar-Pobuda, Xian Hu, Diana L. Bordin, Judith Staerk, Eivind Valen, Bernhard Schmierer, Markku Varjosalo, Jussi Taipale, Emma Haapaniemi
Summary: Precision CRISPR gene editing can be improved by fusing DNA repair proteins with Cas9, with different fusion proteins showing varying effects based on cell type and genomic site. Optimization is necessary to account for the diverse factors contributing to locus-specific genome editing outcomes.
Review
Pharmacology & Pharmacy
Juliana Popovitz, Rohit Sharma, Reyhane Hoshyar, Beob Soo Kim, Niren Murthy, Kunwoo Lee
Summary: The field of gene editing has been the subject of significant attention due to its potential for therapeutic applications. This review focuses on the use of mRNA delivery for gene editing therapeutics and discusses the engineering and improvement of gene editing technology. It also examines ex vivo and in vivo gene editing techniques and explores the future of CRISPR and base editing systems.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Engineering, Biomedical
Marcelo Calderon, Sarah Hedtrich
Summary: This article discusses the design and biological assessment of delivery systems for gene editing tools like CRISPR in skin and mucosal surfaces, highlighting the current state-of-the-art, current knowledge, and translational gaps towards improved translation.
ADVANCED HEALTHCARE MATERIALS
(2021)