{"topic":"gene-editing-therapies","sort":"top","limit":25,"offset":0,"count":25,"papers":[{"id":"doi:10.1038/s41565-020-0669-6","kind":"article","title":"Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing","authors":["Qiang Cheng","Tuo Wei","Lukas Farbiak","Lindsay T. Johnson","Sean A. Dilliard","Daniel J. Siegwart"],"author_count":6,"year":2020,"published":"2020-04-01","venue":"Nature Nanotechnology","cited_by":2370,"doi":"10.1038/s41565-020-0669-6","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41565-020-0669-6","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41565-020-0669-6","updated":null,"pmid":"32251383","pmcid":null,"openalex_id":"W3015140168","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["RNA Interference and Gene Delivery"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1056/nejmoa2031054","kind":"article","title":"CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia","authors":["Haydar Frangoul","David Altshuler","Maria Domenica Cappellini","Yi-Shan Chen","Jennifer Domm","Brenda K. Eustace","Juergen L. Foell","Josu de la Fuente","Stephan A. Grupp","Rupert Handgretinger","Tony W. Ho","Antonis Kattamis","Andrew M. Kernytsky","Julie A. Lekstrom-Himes","Amanda M. Li","Franco Locatelli","Markus Y. Mapara","Mariane de Montalembert","Damiano Rondelli","Akshay Sharma","Sujit Sheth","Sandeep Soni","Martin H. Steinberg","Donna Ann Wall","Angela Yen"],"author_count":26,"year":2020,"published":"2020-12-05","venue":"New England Journal of Medicine","cited_by":1960,"doi":"10.1056/nejmoa2031054","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1056/nejmoa2031054","archive_url":"https://space-kitty.com/papers/doi:10.1056/nejmoa2031054","updated":null,"pmid":"33283989","pmcid":null,"openalex_id":"W3112179900","pdf_url":"https://www.nejm.org/doi/pdf/10.1056/NEJMoa2031054?articleTools=true","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Hemoglobinopathies and Related Disorders"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41392-019-0089-y","kind":"review","title":"Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects","authors":["Hongyi Li","Yang Yang","Weiqi Hong","Mengyuan Huang","Min Wu","Xia Zhao"],"author_count":6,"year":2020,"published":"2020-01-03","venue":"Signal Transduction and Targeted Therapy","cited_by":1720,"doi":"10.1038/s41392-019-0089-y","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41392-019-0089-y","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41392-019-0089-y","updated":null,"pmid":"32296011","pmcid":null,"openalex_id":"W2998881619","pdf_url":"https://www.nature.com/articles/s41392-019-0089-y.pdf","abstract":"Based on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects\" by Hongyi Li, Yang Yang, Weiqi Hong et al., https://doi.org/10.1038/s41392-019-0089-y, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1186/s13756-019-0533-3","kind":"review","title":"Antibiotics versus biofilm: an emerging battleground in microbial communities","authors":["Divakar Sharma","Lama Misba","Asad Ullah Khan"],"author_count":3,"year":2019,"published":"2019-05-16","venue":"Antimicrobial Resistance and Infection Control","cited_by":1560,"doi":"10.1186/s13756-019-0533-3","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1186/s13756-019-0533-3","archive_url":"https://space-kitty.com/papers/doi:10.1186/s13756-019-0533-3","updated":null,"pmid":"31131107","pmcid":null,"openalex_id":"W2946458716","pdf_url":"https://aricjournal.biomedcentral.com/track/pdf/10.1186/s13756-019-0533-3","abstract":"Biofilm is a complex structure of microbiome having different bacterial colonies or single type of cells in a group; adhere to the surface. These cells are embedded in extracellular polymeric substances, a matrix which is generally composed of eDNA, proteins and polysaccharides, showed high resistance to antibiotics. It is one of the major causes of infection persistence especially in nosocomial settings through indwelling devices. Quorum sensing plays an important role in regulating the biofilm formation. There are many approaches being used to control infections by suppressing its formation but CRISPR-CAS (gene editing technique) and photo dynamic therapy (PDT) are proposed to be used as therapeutic approaches to subside bacterial biofim infections, especially caused by deadly drug resistant bad bugs.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Bacterial biofilms and quorum sensing"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Antibiotics versus biofilm: an emerging battleground in microbial communities\" by Divakar Sharma, Lama Misba, Asad Ullah Khan, https://doi.org/10.1186/s13756-019-0533-3, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1073/pnas.1420294112","kind":"article","title":"Boosting CRISPR/Cas9 multiplex editing capability with the endogenous tRNA-processing system","authors":["Kabin Xie","Bastian Minkenberg","Yinong Yang"],"author_count":3,"year":2015,"published":"2015-03-02","venue":"Proceedings of the National Academy of Sciences","cited_by":1555,"doi":"10.1073/pnas.1420294112","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1073/pnas.1420294112","archive_url":"https://space-kitty.com/papers/doi:10.1073/pnas.1420294112","updated":null,"pmid":"25733849","pmcid":null,"openalex_id":"W1992783297","pdf_url":"https://www.pnas.org/content/pnas/112/11/3570.full.pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41580-019-0131-5","kind":"review","title":"The next generation of CRISPR–Cas technologies and applications","authors":["Adrian Pickar‐Oliver","Charles A. Gersbach"],"author_count":2,"year":2019,"published":"2019-05-30","venue":"Nature Reviews Molecular Cell Biology","cited_by":1459,"doi":"10.1038/s41580-019-0131-5","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41580-019-0131-5","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41580-019-0131-5","updated":null,"pmid":"31147612","pmcid":null,"openalex_id":"W2947777875","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1016/j.cell.2021.09.018","kind":"article","title":"Enhanced prime editing systems by manipulating cellular determinants of editing outcomes","authors":["Chen PJ","Hussmann JA","Yan J","Knipping F","Ravisankar P","Chen PF","Chen C","Nelson JW","Newby GA","Sahin M","Osborn MJ","Weissman JS","Adamson B","Liu DR"],"author_count":14,"year":2021,"published":"2021-10-14","venue":"Cell","cited_by":740,"doi":"10.1016/j.cell.2021.09.018","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2021.09.018","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2021.09.018","updated":null,"pmid":"34653350","pmcid":"PMC8584034","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC8584034/pdf","abstract":"While prime editing enables precise sequence changes in DNA, cellular determinants of prime editing remain poorly understood. Using pooled CRISPRi screens, we discovered that DNA mismatch repair (MMR) impedes prime editing and promotes undesired indel byproducts. We developed PE4 and PE5 prime editing systems in which transient expression of an engineered MMR-inhibiting protein enhances the efficiency of substitution, small insertion, and small deletion prime edits by an average 7.7-fold and 2.0-fold compared to PE2 and PE3 systems, respectively, while improving edit/indel ratios by 3.4-fold in MMR-proficient cell types. Strategic installation of silent mutations near the intended edit can enhance prime editing outcomes by evading MMR. Prime editor protein optimization resulted in a PEmax architecture that enhances editing efficacy by 2.8-fold on average in HeLa cells. These findings enrich our understanding of prime editing and establish prime editing systems that show substantial improvement across 191 edits in seven mammalian cell types.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Enhanced prime editing systems by manipulating cellular determinants of editing outcomes\" by Chen PJ, Hussmann JA, Yan J et al., https://doi.org/10.1016/j.cell.2021.09.018, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/nbt.2654","kind":"article","title":"Multiplex and homologous recombination–mediated genome editing in Arabidopsis and Nicotiana benthamiana using guide RNA and Cas9","authors":["Jianfeng Li","Julie Erin Norville","John Aach","Matthew McCormack","Dandan Zhang","Jenifer Bush","George McDonald Church","Jen Sheen"],"author_count":8,"year":2013,"published":"2013-08-01","venue":"Nature Biotechnology","cited_by":1511,"doi":"10.1038/nbt.2654","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/nbt.2654","archive_url":"https://space-kitty.com/papers/doi:10.1038/nbt.2654","updated":null,"pmid":"23929339","pmcid":null,"openalex_id":"W2021767455","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1016/j.cell.2021.12.021","kind":"article","title":"Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins","authors":["Banskota S","Raguram A","Suh S","Du SW","Davis JR","Choi EH","Wang X","Nielsen SC","Newby GA","Randolph PB","Osborn MJ","Musunuru K","Palczewski K","Liu DR"],"author_count":14,"year":2022,"published":"2022-01-11","venue":"Cell","cited_by":562,"doi":"10.1016/j.cell.2021.12.021","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2021.12.021","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2021.12.021","updated":null,"pmid":"35021064","pmcid":"PMC8809250","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC8809250/pdf","abstract":"Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package and deliver base editor or Cas9 ribonucleoproteins. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient base editing in several primary mouse and human cell types. Using different glycoproteins in eVLPs alters their cellular tropism. Single injections of eVLPs into mice support therapeutic levels of base editing in multiple tissues, reducing serum Pcsk9 levels 78% following 63% liver editing, and partially restoring visual function in a mouse model of genetic blindness. In vitro and in vivo off-target editing from eVLPs was virtually undetected, an improvement over AAV or plasmid delivery. These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and nonviral delivery.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins\" by Banskota S, Raguram A, Suh S et al., https://doi.org/10.1016/j.cell.2021.12.021, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1080/10717544.2018.1474964","kind":"review","title":"Delivering CRISPR: a review of the challenges and approaches","authors":["Christopher A. Lino","Jason C. Harper","James P. Carney","Jerilyn A. Timlin"],"author_count":4,"year":2018,"published":"2018-01-01","venue":"Drug Delivery","cited_by":1184,"doi":"10.1080/10717544.2018.1474964","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1080/10717544.2018.1474964","archive_url":"https://space-kitty.com/papers/doi:10.1080/10717544.2018.1474964","updated":null,"pmid":"29801422","pmcid":null,"openalex_id":"W2804566227","pdf_url":null,"abstract":"Gene therapy has long held promise to correct a variety of human diseases and defects. Discovery of the Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR), the mechanism of the CRISPR-based prokaryotic adaptive immune system (CRISPR-associated system, Cas), and its repurposing into a potent gene editing tool has revolutionized the field of molecular biology and generated excitement for new and improved gene therapies. Additionally, the simplicity and flexibility of the CRISPR/Cas9 site-specific nuclease system has led to its widespread use in many biological research areas including development of model cell lines, discovering mechanisms of disease, identifying disease targets, development of transgene animals and plants, and transcriptional modulation. In this review, we present the brief history and basic mechanisms of the CRISPR/Cas9 system and its predecessors (ZFNs and TALENs), lessons learned from past human gene therapy efforts, and recent modifications of CRISPR/Cas9 to provide functions beyond gene editing. We introduce several factors that influence CRISPR/Cas9 efficacy which must be addressed before effective in vivo human gene therapy can be realized. The focus then turns to the most difficult barrier to potential in vivo use of CRISPR/Cas9, delivery. We detail the various cargos and delivery vehicles reported for CRISPR/Cas9, including physical delivery methods (e.g. microinjection; electroporation), viral delivery methods (e.g. adeno-associated virus (AAV); full-sized adenovirus and lentivirus), and non-viral delivery methods (e.g. liposomes; polyplexes; gold particles), and discuss their relative merits. We also examine several technologies that, while not currently reported for CRISPR/Cas9 delivery, appear to have promise in this field. The therapeutic potential of CRISPR/Cas9 is vast and will only increase as the technology and its delivery improves.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Delivering CRISPR: a review of the challenges and approaches\" by Christopher A. Lino, Jason C. Harper, James P. Carney et al., https://doi.org/10.1080/10717544.2018.1474964, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/nature20565","kind":"article","title":"In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration","authors":["Keiichiro Suzuki","Yuji Tsunekawa","Reyna Hernández‐Benítez","Jun Wu","Jie Zhu","Euiseok J. Kim","Fumiyuki Hatanaka","Mako Yamamoto","Toshikazu Araoka","Zhe Li","Masakazu Kurita","Tomoaki Hishida","Mo Li","Emi Aizawa","Shicheng Guo","Song Chen","April M. Goebl","Rupa Devi Soligalla","Jing Tao Qu","Ting-Shuai Jiang","Xin Fu","Maryam Jafari","Concepción Rodrı́guez Esteban","W. Travis Berggren","Jerónimo Lajara"],"author_count":35,"year":2016,"published":"2016-11-15","venue":"Nature","cited_by":1149,"doi":"10.1038/nature20565","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/nature20565","archive_url":"https://space-kitty.com/papers/doi:10.1038/nature20565","updated":null,"pmid":"27851729","pmcid":null,"openalex_id":"W2550079706","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1126/science.aad5143","kind":"article","title":"In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy","authors":["Christopher E. Nelson","Chady H. Hakim","David G. Ousterout","Pratiksha I. Thakore","Eirik A. Moreb","Ruth M. Castellanos Rivera","Sarina Madhavan","Xiufang Pan","F. Ann Ran","Winston X. Yan","Aravind Asokan","Feng Zhang","Dongsheng Duan","Charles A. Gersbach"],"author_count":14,"year":2015,"published":"2015-12-31","venue":"Science","cited_by":1143,"doi":"10.1126/science.aad5143","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1126/science.aad5143","archive_url":"https://space-kitty.com/papers/doi:10.1126/science.aad5143","updated":null,"pmid":"26721684","pmcid":null,"openalex_id":"W2208696160","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1016/j.cell.2022.03.045","kind":"review","title":"Therapeutic in vivo delivery of gene editing agents","authors":["Raguram A","Banskota S","Liu DR"],"author_count":3,"year":2022,"published":"2022-07-06","venue":"Cell","cited_by":459,"doi":"10.1016/j.cell.2022.03.045","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2022.03.045","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2022.03.045","updated":null,"pmid":"35798006","pmcid":"PMC9454337","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC9454337/pdf","abstract":"In vivo gene editing therapies offer the potential to treat the root causes of many genetic diseases. Realizing the promise of therapeutic in vivo gene editing requires the ability to safely and efficiently deliver gene editing agents to relevant organs and tissues in vivo. Here, we review current delivery technologies that have been used to enable therapeutic in vivo gene editing, including viral vectors, lipid nanoparticles, and virus-like particles. Since no single delivery modality is likely to be appropriate for every possible application, we compare the benefits and drawbacks of each method and highlight opportunities for future improvements.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Therapeutic in vivo delivery of gene editing agents\" by Raguram A, Banskota S, Liu DR, https://doi.org/10.1016/j.cell.2022.03.045, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/nbt.3659","kind":"article","title":"Applications of CRISPR technologies in research and beyond","authors":["Rodolphe Barrangou","Jennifer A. Doudna"],"author_count":2,"year":2016,"published":"2016-09-01","venue":"Nature Biotechnology","cited_by":1004,"doi":"10.1038/nbt.3659","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/nbt.3659","archive_url":"https://space-kitty.com/papers/doi:10.1038/nbt.3659","updated":null,"pmid":"27606440","pmcid":null,"openalex_id":"W2511569157","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41591-018-0050-6","kind":"article","title":"p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells","authors":["Robert J. Ihry","Kathleen A. Worringer","Max R. Salick","Elizabeth Frias","Daniel J. Ho","Kraig M. Theriault","Sravya Kommineni","Julie Chen","Marie Sondey","Chaoyang Ye","Ranjit Randhawa","Tripti Kulkarni","Zinger Yang","Gregory McAllister","Carsten Russ","John S. Reece-Hoyes","William C. Forrester","Gregory R. Hoffman","Ricardo E. Dolmetsch","Ajamete Kaykas"],"author_count":20,"year":2018,"published":"2018-06-08","venue":"Nature Medicine","cited_by":977,"doi":"10.1038/s41591-018-0050-6","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41591-018-0050-6","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41591-018-0050-6","updated":null,"pmid":"29892062","pmcid":null,"openalex_id":"W2807198924","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2017/07/26/168443.full.pdf","abstract":null,"abstract_license":null,"license":"cc-by-nc-nd","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1016/j.cell.2024.01.042","kind":"review","title":"Past, present, and future of CRISPR genome editing technologies","authors":["Martin Pačesa","Oana Pelea","Martin Jínek"],"author_count":3,"year":2024,"published":"2024-02-01","venue":"Cell","cited_by":607,"doi":"10.1016/j.cell.2024.01.042","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2024.01.042","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2024.01.042","updated":null,"pmid":"38428389","pmcid":null,"openalex_id":"W4392303996","pdf_url":null,"abstract":"Genome editing has been a transformative force in the life sciences and human medicine, offering unprecedented opportunities to dissect complex biological processes and treat the underlying causes of many genetic diseases. CRISPR-based technologies, with their remarkable efficiency and easy programmability, stand at the forefront of this revolution. In this Review, we discuss the current state of CRISPR gene editing technologies in both research and therapy, highlighting limitations that constrain them and the technological innovations that have been developed in recent years to address them. Additionally, we examine and summarize the current landscape of gene editing applications in the context of human health and therapeutics. Finally, we outline potential future developments that could shape gene editing technologies and their applications in the coming years.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Past, present, and future of CRISPR genome editing technologies\" by Martin Pačesa, Oana Pelea, Martin Jínek, https://doi.org/10.1016/j.cell.2024.01.042, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1002/advs.201700611","kind":"article","title":"Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs","authors":["Lin Y","Wu J","Gu W","Huang Y","Tong Z","Huang L","Tan J"],"author_count":7,"year":2018,"published":"2018-01-30","venue":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","cited_by":493,"doi":"10.1002/advs.201700611","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1002/advs.201700611","archive_url":"https://space-kitty.com/papers/doi:10.1002/advs.201700611","updated":null,"pmid":"29721412","pmcid":"PMC5908366","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5908366/pdf","abstract":"Targeted delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system to the receptor cells is essential for in vivo gene editing. Exosomes are intensively studied as a promising targeted drug delivery carrier recently, while limited by their low efficiency in encapsulating of large nucleic acids. Here, a kind of hybrid exosomes with liposomes is developed via simple incubation. Different from the original exosomes, the resultant hybrid nanoparticles efficiently encapsulate large plasmids, including the CRISPR-Cas9 expression vectors, similarly as the liposomes. Moreover, the resultant hybrid nanoparticles can be endocytosed by and express the encapsulated genes in the mesenchymal stem cells (MSCs), which cannot be transfected by the liposome alone. Taken together, the exosome-liposome hybrid nanoparticles can deliver CRISPR-Cas9 system in MSCs and thus be promising in in vivo gene manipulation.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs\" by Lin Y, Wu J, Gu W et al., https://doi.org/10.1002/advs.201700611, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1158/1078-0432.ccr-16-1300","kind":"article","title":"Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition","authors":["Jiangtao Ren","Xiaojun Liu","Chongyun Fang","Shuguang Jiang","Carl H. June","Yangbing Zhao"],"author_count":6,"year":2016,"published":"2016-11-04","venue":"Clinical Cancer Research","cited_by":941,"doi":"10.1158/1078-0432.ccr-16-1300","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1158/1078-0432.ccr-16-1300","archive_url":"https://space-kitty.com/papers/doi:10.1158/1078-0432.ccr-16-1300","updated":null,"pmid":"27815355","pmcid":null,"openalex_id":"W2548694234","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CAR-T cell therapy research"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.3389/fbioe.2023.1143157","kind":"review","title":"Off-target effects in CRISPR/Cas9 gene editing","authors":["Congting Guo","Xiaoteng Ma","Fei Gao","Yuxuan Guo"],"author_count":4,"year":2023,"published":"2023-03-09","venue":"Frontiers in Bioengineering and Biotechnology","cited_by":626,"doi":"10.3389/fbioe.2023.1143157","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.3389/fbioe.2023.1143157","archive_url":"https://space-kitty.com/papers/doi:10.3389/fbioe.2023.1143157","updated":null,"pmid":"36970624","pmcid":null,"openalex_id":"W4323666400","pdf_url":"https://www.frontiersin.org/articles/10.3389/fbioe.2023.1143157/pdf","abstract":"Gene editing stands for the methods to precisely make changes to a specific nucleic acid sequence. With the recent development of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, gene editing has become efficient, convenient and programmable, leading to promising translational studies and clinical trials for both genetic and non-genetic diseases. A major concern in the applications of the CRISPR/Cas9 system is about its off-target effects, namely the deposition of unexpected, unwanted, or even adverse alterations to the genome. To date, many methods have been developed to nominate or detect the off-target sites of CRISPR/Cas9, which laid the basis for the successful upgrades of CRISPR/Cas9 derivatives with enhanced precision. In this review, we summarize these technological advancements and discuss about the current challenges in the management of off-target effects for future gene therapy.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Off-target effects in CRISPR/Cas9 gene editing\" by Congting Guo, Xiaoteng Ma, Fei Gao et al., https://doi.org/10.3389/fbioe.2023.1143157, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/nature20134","kind":"article","title":"CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells","authors":["Daniel P. Dever","Rasmus Otkjær Bak","Andreas Reinisch","Joab Camarena","Gabriel C. Washington","Carmencita E. Nicolas","Mara Pavel-Dinu","Nivi Saxena","Alec B. Wilkens","Sruthi Mantri","Nobuko Uchida","Ayal Hendel","Anupama Narla","Ravindra Majeti","Kenneth I. Weinberg","Matthew Hebden Porteus"],"author_count":16,"year":2016,"published":"2016-11-04","venue":"Nature","cited_by":864,"doi":"10.1038/nature20134","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/nature20134","archive_url":"https://space-kitty.com/papers/doi:10.1038/nature20134","updated":null,"pmid":"27820943","pmcid":null,"openalex_id":"W2547418311","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41587-021-00933-4","kind":"article","title":"In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels","authors":["Rothgangl T","Dennis MK","Lin PJC","Oka R","Witzigmann D","Villiger L","Qi W","Hruzova M","Kissling L","Lenggenhager D","Borrelli C","Egli S","Frey N","Bakker N","Walker JA 2nd","Kadina AP","Victorov DV","Pacesa M","Kreutzer S","Kontarakis Z","Moor A","Jinek M","Weissman D","Stoffel M","van Boxtel R"],"author_count":32,"year":2021,"published":"2021-05-19","venue":"Nature biotechnology","cited_by":352,"doi":"10.1038/s41587-021-00933-4","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41587-021-00933-4","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41587-021-00933-4","updated":null,"pmid":"34012094","pmcid":"PMC8352781","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC8352781/pdf","abstract":"Most known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle-based delivery of mRNA encoding an ABE and a single-guide RNA targeting PCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up to 34% editing (on average, 26%) in macaques. Plasma PCSK9 and LDL levels were stably reduced by 95% and 58% in mice and by 32% and 14% in macaques, respectively. ABE mRNA was cleared rapidly, and no off-target mutations in genomic DNA were found. Re-dosing in macaques did not increase editing, possibly owing to the detected humoral immune response to ABE upon treatment. These findings support further investigation of ABEs to treat patients with monogenic liver diseases.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels\" by Rothgangl T, Dennis MK, Lin PJC et al., https://doi.org/10.1038/s41587-021-00933-4, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.3390/cells8050403","kind":"review","title":"Current Challenges of iPSC-Based Disease Modeling and Therapeutic Implications","authors":["Michael Xavier Doss","Agapios Sachinidis"],"author_count":2,"year":2019,"published":"2019-04-30","venue":"Cells","cited_by":457,"doi":"10.3390/cells8050403","arxiv_id":null,"nct_id":null,"source_url":"http://dx.doi.org/10.3390/cells8050403","archive_url":"https://space-kitty.com/papers/doi:10.3390/cells8050403","updated":null,"pmid":"31052294","pmcid":"PMC6562607","openalex_id":"W2942799604","pdf_url":"https://www.mdpi.com/2073-4409/8/5/403/pdf?version=1556632267","abstract":"Induced pluripotent stem cell (iPSC)-based disease modelling and the cell replacement therapy approach have proven to be very powerful and instrumental in biomedical research and personalized regenerative medicine as evidenced in the past decade by unraveling novel pathological mechanisms of a multitude of monogenic diseases at the cellular level and the ongoing and emerging clinical trials with iPSC-derived cell products. iPSC-based disease modelling has sparked widespread enthusiasm and has presented an unprecedented opportunity in high throughput drug discovery platforms and safety pharmacology in association with three-dimensional multicellular organoids such as personalized organs-on-chips, gene/base editing, artificial intelligence and high throughput \"omics\" methodologies. This critical review summarizes the progress made in the past decade with the advent of iPSC discovery in biomedical applications and regenerative medicine with case examples and the current major challenges that need to be addressed to unleash the full potential of iPSCs in clinical settings and pharmacology for more effective and safer regenerative therapy.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Pluripotent Stem Cells Research"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Current Challenges of iPSC-Based Disease Modeling and Therapeutic Implications\" by Michael Xavier Doss, Agapios Sachinidis, https://doi.org/10.3390/cells8050403, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1016/j.cell.2023.07.039","kind":"article","title":"Phage-assisted evolution and protein engineering yield compact, efficient prime editors","authors":["Doman JL","Pandey S","Neugebauer ME","An M","Davis JR","Randolph PB","McElroy A","Gao XD","Raguram A","Richter MF","Everette KA","Banskota S","Tian K","Tao YA","Tolar J","Osborn MJ","Liu DR"],"author_count":17,"year":2023,"published":"2023-08-01","venue":"Cell","cited_by":286,"doi":"10.1016/j.cell.2023.07.039","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2023.07.039","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2023.07.039","updated":null,"pmid":"37657419","pmcid":"PMC10482982","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC10482982/pdf","abstract":"Prime editing enables a wide variety of precise genome edits in living cells. Here we use protein evolution and engineering to generate prime editors with reduced size and improved efficiency. Using phage-assisted evolution, we improved editing efficiencies of compact reverse transcriptases by up to 22-fold and generated prime editors that are 516-810 base pairs smaller than the current-generation editor PEmax. We discovered that different reverse transcriptases specialize in different types of edits and used this insight to generate reverse transcriptases that outperform PEmax and PEmaxΔRNaseH, the truncated editor used in dual-AAV delivery systems. Finally, we generated Cas9 domains that improve prime editing. These resulting editors (PE6a-g) enhance therapeutically relevant editing in patient-derived fibroblasts and primary human T-cells. PE6 variants also enable longer insertions to be installed in vivo following dual-AAV delivery, achieving 40% loxP insertion in the cortex of the murine brain, a 24-fold improvement compared to previous state-of-the-art prime editors.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Phage-assisted evolution and protein engineering yield compact, efficient prime editors\" by Doman JL, Pandey S, Neugebauer ME et al., https://doi.org/10.1016/j.cell.2023.07.039, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1093/nar/gkw159","kind":"article","title":"Repurposing the CRISPR-Cas9 system for targeted DNA methylation","authors":["Aleksandar Vojta","Paula Dobrinić","Vanja Tadić","Luka Bočkor","Petra Korać","Boris Dominik Jülg","Marija Klasić","Vlatka Zoldoš"],"author_count":8,"year":2016,"published":"2016-03-11","venue":"Nucleic Acids Research","cited_by":780,"doi":"10.1093/nar/gkw159","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1093/nar/gkw159","archive_url":"https://space-kitty.com/papers/doi:10.1093/nar/gkw159","updated":null,"pmid":"26969735","pmcid":null,"openalex_id":"W2294327742","pdf_url":"https://academic.oup.com/nar/article-pdf/44/12/5615/17436386/gkw159.pdf","abstract":null,"abstract_license":null,"license":"cc-by-nc","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CRISPR and Genetic Engineering"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41598-017-00462-8","kind":"article","title":"CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells","authors":["Levi J. Rupp","Kathrin Schumann","Kole T. Roybal","Rachel E. Gate","Chun Ye","Wendell A. Lim","Alexander Marson"],"author_count":7,"year":2017,"published":"2017-04-03","venue":"Scientific Reports","cited_by":757,"doi":"10.1038/s41598-017-00462-8","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41598-017-00462-8","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41598-017-00462-8","updated":null,"pmid":"28389661","pmcid":null,"openalex_id":"W2604982880","pdf_url":"https://www.nature.com/articles/s41598-017-00462-8.pdf","abstract":"Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model. To overcome this suppressed anti-tumor response, we developed a protocol for combined Cas9 ribonucleoprotein (Cas9 RNP)-mediated gene editing and lentiviral transduction to generate PD-1 deficient anti-CD19 CAR T cells. Pdcd1 (PD-1) disruption augmented CAR T cell mediated killing of tumor cells in vitro and enhanced clearance of PD-L1+ tumor xenografts in vivo. This study demonstrates improved therapeutic efficacy of Cas9-edited CAR T cells and highlights the potential of precision genome engineering to enhance next-generation cell therapies.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CAR-T cell therapy research"],"details":null,"provenance":"openalex","attribution":"Abstract of \"CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells\" by Levi J. Rupp, Kathrin Schumann, Kole T. Roybal et al., https://doi.org/10.1038/s41598-017-00462-8, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."}],"next":"https://space-kitty.com/api/v1/topics/gene-editing-therapies/papers?sort=top&limit=25&offset=25"}