Frontiers in genome editing最新文献

{"title":"Editorial: Overcoming genome editing challenges in plants: new tools and nanotechnologies.","authors":"Sachin Rustgi, Huan Zhang, Tufan Mehmet Oz","doi":"10.3389/fgeed.2023.1230424","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1230424","url":null,"abstract":"Genome editing has been an active research area for the last 2 decades (Carroll, 2021). As a result, we have witnessed many breakthroughs, from the development of designer nucleases to their use in microbes, animals, humans, and agricultural plants (Adli, 2018; Zhang et al., 2019; Anzalone et al., 2020; Li et al., 2023; Wang and Doudna, 2023). More recently, to improve the editing accuracy and precision and reduce dependence on the cell’s developmental state, new approaches, such as the OMEGA (obligate mobile element-guided activity), CAST (CRISPR-Cas-associated transposon), and INTEGRATE (insertion of transposable elements by guide RNA-assisted targeting), were developed and tested in different organisms (Tenjo-Castaño et al., 2022). Further, CRISPR technology was deployed in imaging, diagnostics (Wang and Doudna, 2023), and treatment of major human disorders (Wang and Doudna, 2023). Likewise, these technologies were deployed in agriculture to edit all major row crops, such as rice, wheat, maize, cotton, soybean, and horticultural crops like banana, tomato, apple, and poplar, for various traits from disease resistance to consumer preference traits (Zhu et al., 2020; FAO, 2023). Despite the revolutionary nature of genome-editing tools and the notable progress that these tools have enabled in plant improvement, there remain many challenges for the mainstream application of CRISPR technology in many plant species. Most of these challenges stem directly or indirectly from the cargo delivery and tissue culture-based plant regeneration bottlenecks (Rustgi et al.). Recent progress has been made in the delivery area through using nanomaterials and DNA/RNA viruses, along with notable improvements to the tissue culture process via developmental regulators, growth factors, and haploidy inducers, among many other approaches (Rustgi et al.). Given the remarkable amount of research on genome editing, there are still some bottlenecks, making it imperative to summarize the progress and identify areas that need further research. Keeping this goal in mind, we invited research and review papers from the leading research group in this workspace. After the extensive peer-review process, five articles that summarize the depth of the subject area were published. The articles published in this volume are briefly summarized below. OPEN ACCESS","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1230424"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9660024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Genome and transcriptome editing to understand and treat neuromuscular diseases.","authors":"Rika Maruyama, Alyson Fiorillo, Christopher Heier, Dongsheng Duan, Toshifumi Yokota","doi":"10.3389/fgeed.2023.1176699","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1176699","url":null,"abstract":"Neuromuscular diseases such as Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy are debilitating conditions that affect millions of individuals worldwide. In recent years, there has been a growing interest in the use of genome and transcriptome editing techniques to understand and treat these diseases. This Research Topic brings together four articles that highlight the latest advances in this field. The first article “A Single Transcript Knockdown-Replacement Strategy Employing 5′ UTR Secondary Structures to Precisely Titrate Rescue Protein Translation” by Millette et al., presents a new strategy for precisely titrating rescue protein translation in cases of diseases caused by coding mutations such as amyotrophic lateral sclerosis (ALS). The authors developed amodular, single-transgene expression system that allows control over translation from high-expression, ubiquitous promoters. This system uses “attenuator” sequences in the 5’UTRwhich predictably diminish the translation of the paired gene, providing wide general utility. The authors also demonstrate that this approach can be used to achieve a knockdown and rescue effect by pairing microRNA-adapted shRNAs alongside their respective replacement gene on a single transcript. They also showed that this approach can be used to replace the SOD1 gene in stable cell lines and demonstrate complete and predictable control over replacement of SOD1 by varying the strength of attenuators. This study highlights the potential utility of this approach in treating monogenic diseases caused by heterogeneous mutations. The second article “Development of Therapeutic RNA Manipulation for Muscular Dystrophy” by Saifullah et al., reviews the current state of therapeutic RNA manipulation for muscular dystrophies, specifically Duchenne muscular dystrophy (DMD). DMD is a severe monogenic disease caused by mutations in the DMD gene, leading to muscle degeneration and atrophy early in life and premature death. This article highlights the potential of oligonucleotide-based therapeutics, specifically exon skipping using antisense oligonucleotides (ASO), as a promising strategy for treating OPEN ACCESS","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1176699"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9220629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-efficiency editing in hematopoietic stem cells and the HUDEP-2 cell line based on <i>in vitro</i> mRNA synthesis.","authors":"Nikoletta Y Papaioannou,&nbsp;Petros Patsali,&nbsp;Basma Naiisseh,&nbsp;Panayiota L Papasavva,&nbsp;Lola Koniali,&nbsp;Ryo Kurita,&nbsp;Yukio Nakamura,&nbsp;Soteroula Christou,&nbsp;Maria Sitarou,&nbsp;Claudio Mussolino,&nbsp;Toni Cathomen,&nbsp;Marina Kleanthous,&nbsp;Carsten W Lederer","doi":"10.3389/fgeed.2023.1141618","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1141618","url":null,"abstract":"<p><p><b>Introduction:</b> Genome editing tools, such as CRISPR/Cas, TALE nucleases and, more recently, double-strand-break-independent editors, have been successfully used for gene therapy and reverse genetics. Among various challenges in the field, tolerable and efficient delivery of editors to target cells and sites, as well as independence from commercially available tools for flexibility and fast adoption of new editing technology are the most pressing. For many hematopoietic research applications, primary CD34⁺ cells and the human umbilical cord-derived progenitor erythroid 2 (HUDEP-2) cell line are highly informative substrates and readily accessible for <i>in vitro</i> manipulation. Moreover, <i>ex vivo</i> editing of CD34⁺ cells has immediate therapeutic relevance. Both cell types are sensitive to standard transfection procedures and reagents, such as lipofection with plasmid DNA, calling for more suitable methodology in order to achieve high efficiency and tolerability of editing with editors of choice. These challenges can be addressed by RNA delivery, either as a mixture of guide RNA and mRNA for CRISRP/Cas-based systems or as a mixture of mRNAs for TALENs. Compared to ribonucleoproteins or proteins, RNA as vector creates flexibility by removing dependence on commercial availability or laborious in-house preparations of novel editor proteins. Compared to DNA, RNA is less toxic and by obviating nuclear transcription and export of mRNA offers faster kinetics and higher editing efficiencies. <b>Methods:</b> Here, we detail an <i>in vitro</i> transcription protocol based on plasmid DNA templates with the addition of Anti-Reverse Cap Analog (ARCA) using T7 RNA polymerase, and poly (A) tailing using poly (A) polymerase, combined with nucleofection of HUDEP-2 and patient-derived CD34⁺ cells. Our protocol for RNA-based delivery employs widely available reagents and equipment and can easily be adopted for universal <i>in vitro</i> delivery of genome editing tools. <b>Results and Discussion:</b> Drawing on a common use case, we employ the protocol to target a β-globin mutation and to reactivate γ-globin expression as two potential therapies for β-hemoglobinopathies, followed by erythroid differentiation and functional analyses. Our protocol allows high editing efficiencies and unimpaired cell viability and differentiation, with scalability, suitability for functional assessment of editing outcomes and high flexibility in the application to different editors.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1141618"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10296309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a genome editing tool using CRISPR-Cas9 ribonucleoprotein complexes in the non-model plant pathogen <i>Sphaerulina musiva</i>.","authors":"Joanna Tannous,&nbsp;Cole Sawyer,&nbsp;Md Mahmudul Hassan,&nbsp;Jesse L Labbe,&nbsp;Carrie Eckert","doi":"10.3389/fgeed.2023.1110279","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1110279","url":null,"abstract":"<p><p>CRISPR-Cas9 is a versatile genome editing system widely used since 2013 to introduce site-specific modifications into the genomes of model and non-model species. This technology is used in various applications, from gene knock-outs, knock-ins, and over-expressions to more precise changes, such as the introduction of nucleotides at a targeted locus. CRISPR-Cas9 has been demonstrated to be easy to establish in new species and highly efficient and specific compared to previous gene editing strategies such as Zinc finger nucleases and transcription activator-like effector nucleases. Grand challenges for emerging CRISPR-Cas9 tools in filamentous fungi are developing efficient transformation methods for non-model organisms. In this paper, we have leveraged the establishment of CRISPR-Cas9 genome editing tool that relies on Cas9/sgRNA ribonucleoprotein complexes (RNPs) in the model species <i>Trichoderma reesei</i> and developed the first protocol to efficiently transform the non-model species, <i>Sphaerulina musiva.</i> This fungal pathogen constitutes a real threat to the genus <i>Populus,</i> a foundational bioenergy crop used for biofuel production. Herein, we highlight the general considerations to design sgRNAs and their computational validation. We also describe the use of isolated protoplasts to deliver the CRISPR-Cas9 RNP components in both species and the screening for targeted genome editing events. The development of engineering tools in <i>S. musiva</i> can be used for studying genes involved in diverse processes such as secondary metabolism, establishment, and pathogenicity, among many others, but also for developing genetic mitigation approaches. The approach described here provides guidance for potential development of transformation systems in other non-model spore-bearing ascomycetes.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1110279"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10308295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient <i>hyperactive piggyBac</i> transgenesis in <i>Plodia</i> pantry moths.","authors":"Christa Heryanto, Anyi Mazo-Vargas, Arnaud Martin","doi":"10.3389/fgeed.2022.1074888","DOIUrl":"10.3389/fgeed.2022.1074888","url":null,"abstract":"<p><p>While <i>piggyBac</i> transposon-based transgenesis is widely used in various emerging model organisms, its relatively low transposition rate in butterflies and moths has hindered its use for routine genetic transformation in Lepidoptera. Here, we tested the suitability of a codon-optimized <i>hyperactive piggyBac</i> transposase (<i>hyPBase</i>) in mRNA form to deliver and integrate transgenic cassettes into the genome of the pantry moth <i>Plodia interpunctella</i>. Co-injection of <i>hyPBase</i> mRNA with donor plasmids successfully integrated 1.5-4.4 kb expression cassettes driving the fluorescent markers EGFP, DsRed, or EYFP in eyes and glia with the <i>3xP3</i> promoter. Somatic integration and expression of the transgene in the G₀ injected generation was detectable from 72-h embryos and onward in larvae, pupae and adults carrying a recessive white-eyed mutation. Overall, 2.5% of injected eggs survived into transgene-bearing adults with mosaic fluorescence. Subsequent outcrossing of fluorescent G₀ founders transmitted single-insertion copies of <i>3xP3::EGFP</i> and <i>3xP3::EYFP</i> and generated stable isogenic lines. Random in-crossing of a small cohort of G₀ founders expressing <i>3xP3::DsRed</i> yielded a stable transgenic line segregating for more than one transgene insertion site. We discuss how <i>hyPBase</i> can be used to generate stable transgenic resources in <i>Plodia</i> and other moths.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"4 ","pages":"1074888"},"PeriodicalIF":4.9,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9816379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10874972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging tools for plant nanobiotechnology.","authors":"Bin Zhao, Zhongxu Luo, Honglu Zhang, Huan Zhang","doi":"10.3389/fgeed.2022.1029944","DOIUrl":"10.3389/fgeed.2022.1029944","url":null,"abstract":"<p><p>The successful application of nanobiotechnology in biomedicine has greatly changed the traditional way of diagnosis and treating of disease, and is promising for revolutionizing the traditional plant nanobiotechnology. Over the past few years, nanobiotechnology has increasingly expanded into plant research area. Nanomaterials can be designed as vectors for targeted delivery and controlled release of fertilizers, pesticides, herbicides, nucleotides, proteins, etc. Interestingly, nanomaterials with unique physical and chemical properties can directly affect plant growth and development; improve plant resistance to disease and stress; design as sensors in plant biology; and even be used for plant genetic engineering. Similarly, there have been concerns about the potential biological toxicity of nanomaterials. Selecting appropriate characterization methods will help understand how nanomaterials interact with plants and promote advances in plant nanobiotechnology. However, there are relatively few reviews of tools for characterizing nanomaterials in plant nanobiotechnology. In this review, we present relevant imaging tools that have been used in plant nanobiotechnology to monitor nanomaterial migration, interaction with and internalization into plants at three-dimensional lengths. Including: 1) Migration of nanomaterial into plant organs 2) Penetration of nanomaterial into plant tissues (iii)Internalization of nanomaterials by plant cells and interactions with plant subcellular structures. We compare the advantages and disadvantages of current characterization tools and propose future optimal characterization methods for plant nanobiotechnology.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"4 ","pages":"1029944"},"PeriodicalIF":4.9,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10436908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR nuclease off-target activity and mitigation strategies.","authors":"Beeke Wienert, M Kyle Cromer","doi":"10.3389/fgeed.2022.1050507","DOIUrl":"10.3389/fgeed.2022.1050507","url":null,"abstract":"<p><p>The discovery of CRISPR has allowed site-specific genomic modification to become a reality and this technology is now being applied in a number of human clinical trials. While this technology has demonstrated impressive efficacy in the clinic to date, there remains the potential for unintended on- and off-target effects of CRISPR nuclease activity. A variety of <i>in silico</i>-based prediction tools and empirically derived experimental methods have been developed to identify the most common unintended effect-small insertions and deletions at genomic sites with homology to the guide RNA. However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field. In this review we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence. In addition, many of the current clinical trials using CRISPR involve <i>ex vivo</i> isolation of a patient's own stem cells, modification, and re-transplantation. However, there is growing interest in direct, <i>in vivo</i> delivery of genome editing tools. While this strategy has the potential to address disease in cell types that are not amenable to <i>ex vivo</i> manipulation, <i>in vivo</i> editing has only one desired outcome-on-target editing in the cell type of interest. CRISPR activity in unintended cell types (both on- and off-target) is therefore a major safety as well as ethical concern in tissues that could enable germline transmission. In this review, we have summarized the strengths and weaknesses of current editing and delivery tools and potential improvements to off-target and off-tissue CRISPR activity detection. We have also outlined potential mitigation strategies that will ensure that the safety of CRISPR keeps pace with efficacy, a necessary requirement if this technology is to realize its full translational potential.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"4 ","pages":"1050507"},"PeriodicalIF":4.9,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10658011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant biomacromolecule delivery methods in the 21st century.","authors":"Sachin Rustgi, Salman Naveed, Jonathan Windham, Huan Zhang, Gözde S Demirer","doi":"10.3389/fgeed.2022.1011934","DOIUrl":"10.3389/fgeed.2022.1011934","url":null,"abstract":"<p><p>The 21st century witnessed a boom in plant genomics and gene characterization studies through RNA interference and site-directed mutagenesis. Specifically, the last 15 years marked a rapid increase in discovering and implementing different genome editing techniques. Methods to deliver gene editing reagents have also attempted to keep pace with the discovery and implementation of gene editing tools in plants. As a result, various transient/stable, quick/lengthy, expensive (requiring specialized equipment)/inexpensive, and versatile/specific (species, developmental stage, or tissue) methods were developed. A brief account of these methods with emphasis on recent developments is provided in this review article. Additionally, the strengths and limitations of each method are listed to allow the reader to select the most appropriate method for their specific studies. Finally, a perspective for future developments and needs in this research area is presented.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"4 ","pages":"1011934"},"PeriodicalIF":4.9,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9176663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enabling Genome Editing for Enhanced Agricultural Sustainability","authors":"F. Keiper, A. Atanassova","doi":"10.3389/fgeed.2022.898950","DOIUrl":"https://doi.org/10.3389/fgeed.2022.898950","url":null,"abstract":"Agricultural sustainability encompasses environmental, social, and economic aspects, all of which are continually shifting due changing environmental pressures and societal expectations. A range of strategies are required to address these challenges, and these include the use of innovation and adoption of the best available practices and technologies. Advances in biotechnologies, including genome editing, and their application in plant breeding and research are expected to provide a range of benefits that contribute to all aspects of agricultural sustainability. However, adoption of these technologies needs to be supported by proportionate, coherent, forward-looking, and adaptable policies and regulatory approaches. In this Perspective, we reflect on the regulatory challenges associated with commercialising a transgenic crop, and developments thus far in providing regulatory clarity for genome edited crops. We aim to demonstrate that much remains to be done to shift towards a more proportionate and enabling approach before the potential benefits of genome edited crops can be realised. The implications of precautionary and disproportionate regulation are also discussed.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42310432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advantages and Limitations of Gene Therapy and Gene Editing for Friedreich's Ataxia.","authors":"Anusha Sivakumar, Stephanie Cherqui","doi":"10.3389/fgeed.2022.903139","DOIUrl":"10.3389/fgeed.2022.903139","url":null,"abstract":"<p><p>Friedreich's ataxia (FRDA) is an inherited, multisystemic disorder predominantly caused by GAA hyper expansion in intron 1 of frataxin (<i>FXN</i>) gene. This expansion mutation transcriptionally represses <i>FXN</i>, a mitochondrial protein that is required for iron metabolism and mitochondrial homeostasis, leading to neurodegerative and cardiac dysfunction. Current therapeutic options for FRDA are focused on improving mitochondrial function and increasing frataxin expression through pharmacological interventions but are not effective in delaying or preventing the neurodegeneration in clinical trials. Recent research on <i>in vivo</i> and <i>ex vivo</i> gene therapy methods in FRDA animal and cell models showcase its promise as a one-time therapy for FRDA. In this review, we provide an overview on the current and emerging prospects of gene therapy for FRDA, with specific focus on advantages of CRISPR/Cas9-mediated gene editing of <i>FXN</i> as a viable option to restore endogenous frataxin expression. We also assess the potential of <i>ex vivo</i> gene editing in hematopoietic stem and progenitor cells as a potential autologous transplantation therapeutic option and discuss its advantages in tackling FRDA-specific safety aspects for clinical translation.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"4 ","pages":"903139"},"PeriodicalIF":5.4,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}