CRISPR Journal最新文献_第7页

Genome Editing Therapy for the Blood: Ex Vivo Success and In Vivo Prospects. 血液基因组编辑疗法：体内成功与体内前景。

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-10-01 Epub Date: 2024-09-26 DOI: 10.1089/crispr.2024.0036

Christy A George, Srishti U Sahu, Lorena de Oñate, Bruno Solano de Freitas Souza, Ross C Wilson

{"title":"Genome Editing Therapy for the Blood: Ex Vivo Success and In Vivo Prospects.","authors":"Christy A George, Srishti U Sahu, Lorena de Oñate, Bruno Solano de Freitas Souza, Ross C Wilson","doi":"10.1089/crispr.2024.0036","DOIUrl":"10.1089/crispr.2024.0036","url":null,"abstract":"Hematopoietic stem cells (HSCs) provide the body with a continuous supply of healthy, functional blood cells. In patients with hematopoietic malignancies, immunodeficiencies, lysosomal storage disorders, and hemoglobinopathies, therapeutic genome editing offers hope for corrective intervention, with even modest editing efficiencies likely to provide clinical benefit. Engineered white blood cells, such as T cells, can be applied therapeutically to address monogenic disorders of the immune system, HIV infection, or cancer. The versatility of CRISPR-based tools allows countless new medical interventions for diseases of the blood, and rapid ex vivo success has been demonstrated in hemoglobinopathies via transplantation of the patient's HSCs following genome editing in a laboratory setting. Here we review recent advances in therapeutic genome editing of HSCs and T cells, focusing on the progress in ex vivo contexts, the promise of improved access via in vivo delivery, as well as the ongoing preclinical efforts that may enable the transition from ex vivo to in vivo administration. We discuss the challenges, limitations, and future prospects of this rapidly developing field, which may one day establish CRISPR as the standard of care for some diseases affecting the blood.","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":"231-248"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for The CRISPR Journal. 罗莎琳德-富兰克林学会自豪地宣布《CRISPR 期刊》2023 年度获奖者。

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-10-01 DOI: 10.1089/crispr.2024.55675.rfs2023

Suchita Nety

引用次数: 0

Comparison of Gene-Editing Approaches for Severe Congenital Neutropenia-Causing Mutations in the ELANE Gene. 比较针对 ELANE 基因中导致严重先天性中性粒细胞减少症突变的基因编辑方法

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-10-01 DOI: 10.1089/crispr.2024.0006

Malte Ulrich Ritter, Masoud Nasri, Benjamin Dannenmann, Perihan Mir, Benjamin Secker, Diana Amend, Maksim Klimiankou, Karl Welte, Julia Skokowa

{"title":"Comparison of Gene-Editing Approaches for Severe Congenital Neutropenia-Causing Mutations in the ELANE Gene.","authors":"Malte Ulrich Ritter, Masoud Nasri, Benjamin Dannenmann, Perihan Mir, Benjamin Secker, Diana Amend, Maksim Klimiankou, Karl Welte, Julia Skokowa","doi":"10.1089/crispr.2024.0006","DOIUrl":"10.1089/crispr.2024.0006","url":null,"abstract":"Safety considerations for gene therapies of inherited preleukemia syndromes, including severe congenital neutropenia (CN), are paramount. We compared several strategies for CRISPR/Cas9 gene editing of autosomal-dominant ELANE mutations in CD34+ cells from two CN patients head-to-head. We tested universal and allele-specific ELANE knockout, ELANE mutation correction by homology-directed repair (HDR) with AAV6, and allele-specific HDR with ssODN. All strategies were not toxic, had at least 30% editing, and rescued granulopoiesis in vitro. In contrast to published data, allele-specific indels in the last exon of ELANE also restored granulopoiesis. Moreover, by implementing patient-derived induced pluripotent stem cells for GUIDE-Seq off-target analysis, we established a clinically relevant \"personalized\" assessment of off-target activity of gene editing on the background of the patient's genome. We found that allele-specific approaches had the most favorable off-target profiles. Taken together, a well-defined head-to-head comparison pipeline for selecting the appropriate gene therapy is essential for diseases, with several gene editing strategies available.","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":"7 5","pages":"258-271"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Give Cas a Chance: An Actionable Path to a Platform for CRISPR Cures. 给 Cas 一个机会：通往 CRISPR 治疗平台的可行之路。

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-10-01 DOI: 10.1089/crispr.2024.0082

Fyodor D Urnov

引用次数: 0

Affordable Pricing of CRISPR Treatments is a Pressing Ethical Imperative. CRISPR 治疗的平价化是迫在眉睫的伦理当务之急。

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-10-01 Epub Date: 2024-10-10 DOI: 10.1089/crispr.2024.0042

Jon Rueda, Íñigo de Miguel Beriain, Lluis Montoliu

引用次数: 0

Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for The CRISPR Journal. 罗莎琳德-富兰克林学会自豪地宣布《CRISPR 期刊》2023 年度获奖者。

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-10-01 DOI: 10.1089/crispr.2024.55675.rfs2023

Suchita Nety

引用次数: 0

Enrichment of Allelic Editing Outcomes by Prime Editing in Induced Pluripotent Stem Cells. 通过在诱导多能干细胞中进行基质编辑，丰富等位基因编辑结果。

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-10-01 DOI: 10.1089/crispr.2024.0028

Ryo Niwa, Tomoko Matsumoto, Alexander Y Liu, Maki Kawato, Takayuki Kondo, Kayoko Tsukita, Peter Gee, Haruhisa Inoue, Thomas L Maurissen, Knut Woltjen

引用次数: 0

Widespread Impact of Natural Genetic Variations in CRISPR-Cas9 Outcomes. 自然基因变异对 CRISPR-Cas9 结果的广泛影响。

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-10-01 DOI: 10.1089/crispr.2024.0020

Victoria R Li, Tinghui Wu, Alicja Tadych, Aaron Wong, Zijun Zhang

{"title":"Widespread Impact of Natural Genetic Variations in CRISPR-Cas9 Outcomes.","authors":"Victoria R Li, Tinghui Wu, Alicja Tadych, Aaron Wong, Zijun Zhang","doi":"10.1089/crispr.2024.0020","DOIUrl":"10.1089/crispr.2024.0020","url":null,"abstract":"The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) is a genome editing tool widely used in biological research and clinical therapeutics. Natural human genetic variations, through altering the sequence context of CRISPR-Cas9 target regions, can significantly affect its DNA repair outcomes and ultimately lead to different editing efficiencies. However, these effects have not been systematically studied, even as CRISPR-Cas9 is broadly applied to primary cells and patient samples that harbor such genetic diversity. Here, we present comprehensive investigations of natural genetic variations on CRISPR-Cas9 outcomes across the human genome. The utility of our analysis is illustrated in two case studies, on both preclinical discoveries of CD33 knockout in chimeric antigen receptor-T cell therapy and clinical applications of transthyretin (TTR) inactivation for treating TTR amyloidosis. We further expand our analysis to genome-scale, population-stratified common variants that may lead to gene editing disparity. Our analyses demonstrate pitfalls of failing to account for the widespread genetic variations in Cas9 target selection and how they can be effectively examined and avoided using our method. To facilitate broad access to our analysis, a web platform CROTONdb is developed, which provides predictions for all possible CRISPR-Cas9 target sites in the coding and noncoding regulatory regions, spanning over 5.38 million guide RNA targets and 90.82 million estimated variant effects. We anticipate CROTONdb having broad clinical utilities in gene and cellular therapies.","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":"7 5","pages":"283-292"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenging the Boundaries Between Treatment, Prevention, and Enhancement in Human Genome Editing. 挑战人类基因组编辑中治疗、预防和增强之间的界限。

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-08-01 Epub Date: 2024-07-08 DOI: 10.1089/crispr.2024.0021

Margaret Waltz, Rebecca L Walker, Michael A Flatt, Douglas MacKay, John M Conley, Eric T Juengst, R Jean Cadigan

{"title":"Challenging the Boundaries Between Treatment, Prevention, and Enhancement in Human Genome Editing.","authors":"Margaret Waltz, Rebecca L Walker, Michael A Flatt, Douglas MacKay, John M Conley, Eric T Juengst, R Jean Cadigan","doi":"10.1089/crispr.2024.0021","DOIUrl":"10.1089/crispr.2024.0021","url":null,"abstract":"Traditional distinctions between treatment and enhancement goals for human genome editing (HGE) have animated oversight considerations, yet these categories have been complicated by the addition of prevention as a possible target for HGE applications. To assess the role these three categories might play in continued HGE governance efforts, we report on interviews with genome editing scientists and governance group members. While some accepted traditional distinctions between treatment and enhancement and rejected the latter as unacceptable, others argued that the concept of enhancement is largely irrelevant or not as morally problematic as suggested. Others described how preventive goals for HGE create gray zones where prevention and enhancement may be difficult to distinguish, which may stymie uses of HGE. We conclude by discussing the governance implications of these various understandings of treatment, prevention, and enhancement as HGE research moves beyond the treatment of serious disease to embrace longer range preventive goals.","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":" ","pages":"180-187"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AI and SynBio Meet CRISPR Heralding a New Genome Editing Era. 人工智能和 SynBio 与 CRISPR 相遇，预示着一个新的基因组编辑时代的到来。

IF 3.7 4区生物学

CRISPR Journal Pub Date : 2024-08-01 DOI: 10.1089/crispr.2024.0063

Rodolphe Barrangou

引用次数: 0