{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T11:51:31Z","timestamp":1781265091943,"version":"3.54.1"},"reference-count":152,"publisher":"IOP Publishing","issue":"40","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/page\/copyright"},{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"name":"Fuzhou University, China"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82117267"],"award-info":[{"award-number":["82117267"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Nanotechnology"],"published-print":{"date-parts":[[2024,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat\/CRISPR-associated nuclease 9 (CRISPR\/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR\/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What\u2019s more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR\/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR\/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer.<\/jats:p>","DOI":"10.1088\/1361-6528\/ad5f33","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T22:20:59Z","timestamp":1720131659000},"page":"402002","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Current application and future perspective of CRISPR\/cas9 gene editing system mediated immune checkpoint for liver cancer treatment"],"prefix":"10.1088","volume":"35","author":[{"given":"Ling-Wu","family":"Tong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Shan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Jing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2060-8887","authenticated-orcid":true,"given":"Jing-Wei","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"nanoad5f33bib1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1097\/CM9.0000000000001474","article-title":"Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020","volume":"134","author":"Cao","year":"2021","journal-title":"Chin. Med. J."},{"key":"nanoad5f33bib2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"nanoad5f33bib3","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1002\/ijc.33313","article-title":"Is it possible to halve the incidence of liver cancer in China by 2050?","volume":"148","author":"Shi","year":"2021","journal-title":"Int. J. Cancer"},{"key":"nanoad5f33bib4","doi-asserted-by":"publisher","DOI":"10.1177\/1073274817744621","article-title":"Liver resection and surgical strategies for management of primary liver cancer","volume":"25","author":"Orcutt","year":"2018","journal-title":"Cancer Control"},{"key":"nanoad5f33bib5","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nrgastro.2016.193","article-title":"Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches","volume":"14","author":"Sapisochin","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"nanoad5f33bib6","doi-asserted-by":"publisher","first-page":"vii1","DOI":"10.1093\/annonc\/mdp281","article-title":"The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 10th World Congress on Gastrointestinal Cancer, Barcelona, 2008","volume":"20","author":"Verslype","year":"2009","journal-title":"Ann. Oncol."},{"key":"nanoad5f33bib7","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1053\/j.gastro.2018.09.051","article-title":"Targeted and immune-based therapies for hepatocellular carcinoma","volume":"156","author":"Greten","year":"2019","journal-title":"Gastroenterology"},{"key":"nanoad5f33bib8","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/s41392-020-00264-x","article-title":"Targeted therapy for hepatocellular carcinoma","volume":"5","author":"Huang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"nanoad5f33bib9","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"key":"nanoad5f33bib10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/0284186X.2018.1555375","article-title":"The pioneers behind immune checkpoint blockers awarded the Nobel Prize in physiology or medicine 2018","volume":"58","author":"Dahl","year":"2019","journal-title":"Acta Oncol."},{"key":"nanoad5f33bib11","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.gendis.2018.10.003","article-title":"2018 Nobel Prize in medicine awarded to cancer immunotherapy: immune checkpoint blockade\u2014A personal account","volume":"5","author":"Zang","year":"2018","journal-title":"Genes Dis."},{"key":"nanoad5f33bib12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2021.188638","article-title":"The progress of immune checkpoint therapy in primary liver cancer","volume":"1876","author":"Zheng","year":"2021","journal-title":"Biochim. Biophys. Acta"},{"key":"nanoad5f33bib13","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1093\/annonc\/mdv383","article-title":"Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies","volume":"26","author":"Naidoo","year":"2015","journal-title":"Ann. Oncol."},{"key":"nanoad5f33bib14","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1001\/jamaoncol.2018.3923","article-title":"Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis","volume":"4","author":"Wang","year":"2018","journal-title":"JAMA Oncol."},{"key":"nanoad5f33bib15","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nrg2749","article-title":"CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea","volume":"11","author":"Marraffini","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"nanoad5f33bib16","doi-asserted-by":"publisher","first-page":"12039","DOI":"10.1093\/nar\/gkx843","article-title":"CRISPR\/Cas9-mediated gene knockout is insensitive to target copy number but is dependent on guide RNA potency and Cas9\/sgRNA threshold expression level","volume":"45","author":"Yuen","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"nanoad5f33bib17","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1038\/cr.2017.81","article-title":"One-step generation of complete gene knockout mice and monkeys by CRISPR\/Cas9-mediated gene editing with multiple sgRNAs","volume":"27","author":"Zuo","year":"2017","journal-title":"Cell Res."},{"key":"nanoad5f33bib18","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/s41392-021-00462-1","article-title":"Nanobody-based chimeric antigen receptor T cells designed by CRISPR\/Cas9 technology for solid tumor immunotherapy","volume":"6","author":"Mo","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"nanoad5f33bib19","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202006003","article-title":"Reprogramming the tumor microenvironment through second-near-infrared-window photothermal genome editing of PD-L1 mediated by supramolecular gold nanorods for enhanced cancer immunotherapy","volume":"33","author":"Tang","year":"2021","journal-title":"Adv. Mater."},{"key":"nanoad5f33bib20","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1093\/nar\/30.2.482","article-title":"A DNA repair system specific for thermophilic Archaea and bacteria predicted by genomic context analysis","volume":"30","author":"Makarova","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"nanoad5f33bib21","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1046\/j.1365-2958.2000.01838.x","article-title":"Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria","volume":"36","author":"Mojica","year":"2000","journal-title":"Mol. Microbiol."},{"key":"nanoad5f33bib22","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.tibtech.2017.07.007","article-title":"Advances in industrial biotechnology using CRISPR-cas systems","volume":"36","author":"Donohoue","year":"2018","journal-title":"Trends Biotechnol."},{"key":"nanoad5f33bib23","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/nrmicro2577","article-title":"Evolution and classification of the CRISPR-Cas systems","volume":"9","author":"Makarova","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"nanoad5f33bib24","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/s00005-016-0427-5","article-title":"CRISPR\/Cas9 immune system as a tool for genome engineering","volume":"65","author":"Hryhorowicz","year":"2017","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"nanoad5f33bib25","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nature10886","article-title":"RNA-guided genetic silencing systems in bacteria and archaea","volume":"482","author":"Wiedenheft","year":"2012","journal-title":"Nature"},{"key":"nanoad5f33bib26","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"nanoad5f33bib27","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247997","article-title":"Structures of Cas9 endonucleases reveal RNA-mediated conformational activation","volume":"343","author":"Jinek","year":"2014","journal-title":"Science"},{"key":"nanoad5f33bib28","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.aad5227","article-title":"Rationally engineered Cas9 nucleases with improved specificity","volume":"351","author":"Slaymaker","year":"2016","journal-title":"Science"},{"key":"nanoad5f33bib29","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/nature09886","article-title":"CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III","volume":"471","author":"Deltcheva","year":"2011","journal-title":"Nature"},{"key":"nanoad5f33bib30","doi-asserted-by":"publisher","first-page":"841","DOI":"10.4161\/rna.24203","article-title":"crRNA and tracrRNA guide Cas9-mediated DNA interference in Streptococcus thermophiles","volume":"10","author":"Karvelis","year":"2013","journal-title":"RNA Biol."},{"key":"nanoad5f33bib31","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protocols"},{"key":"nanoad5f33bib32","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1128\/MCB.21.1.289-297.2001","article-title":"Stimulation of homologous recombination through targeted cleavage by chimeric nucleases","volume":"21","author":"Bibikova","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"nanoad5f33bib33","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1534\/genetics.110.120717","article-title":"Targeting DNA double-strand breaks with TAL effector nucleases","volume":"186","author":"Christian","year":"2010","journal-title":"Genetics"},{"key":"nanoad5f33bib34","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/nbt0805-915","article-title":"The zinc finger nuclease monopoly","volume":"23","author":"Scott","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"nanoad5f33bib35","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.tibtech.2013.04.004","article-title":"3rd 2013 ZFN, TALEN, and CRISPR\/Cas-based methods for genome engineering","volume":"31","author":"Gaj","year":"2013","journal-title":"Trends Biotechnol."},{"key":"nanoad5f33bib36","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1001\/jama.2017.10159","article-title":"Gene editing using CRISPR: why the excitement?","volume":"318","author":"Komaroff","year":"2017","journal-title":"JAMA"},{"key":"nanoad5f33bib37","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/nrd.2016.280","article-title":"Delivery technologies for genome editing","volume":"16","author":"Yin","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"nanoad5f33bib38","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.cell.2014.05.010","article-title":"Development and applications of CRISPR-Cas9 for genome engineering","volume":"157","author":"Hsu","year":"2014","journal-title":"Cell"},{"key":"nanoad5f33bib39","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1038\/nmeth.2649","article-title":"Cas9 as a versatile tool for engineering biology","volume":"10","author":"Mali","year":"2013","journal-title":"Nat. Methods"},{"key":"nanoad5f33bib40","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1007\/s12072-021-10237-z","article-title":"Application of CRISPR-Cas9 based gene editing to study the pathogenesis of colon and liver cancer using organoids","volume":"15","author":"Ramakrishna","year":"2021","journal-title":"Hepatol. Int."},{"key":"nanoad5f33bib41","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12943-022-01565-1","article-title":"CRISPR\/Cas9 and next generation sequencing in the personalized treatment of Cancer","volume":"21","author":"Selvakumar","year":"2022","journal-title":"Mol. Cancer"},{"key":"nanoad5f33bib42","doi-asserted-by":"publisher","first-page":"4681","DOI":"10.1038\/s41467-019-12606-7","article-title":"Genome-wide CRISPR\/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC","volume":"10","author":"Wei","year":"2019","journal-title":"Nat. Commun."},{"key":"nanoad5f33bib43","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1136\/jmedgenet-2018-105422","article-title":"Applications and advances of CRISPR-Cas9 in cancer immunotherapy","volume":"56","author":"Xia","year":"2019","journal-title":"J. Med. Genet."},{"key":"nanoad5f33bib44","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"nanoad5f33bib45","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1093\/annonc\/mdx686","article-title":"Mechanistic overview of immune checkpoints to support the rational design of their combinations in cancer immunotherapy","volume":"29","author":"Rotte","year":"2018","journal-title":"Ann. Oncol."},{"key":"nanoad5f33bib46","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/s0952-7915(99)80046-6","article-title":"T cell co-stimulatory molecules other than CD28","volume":"11","author":"Watts","year":"1999","journal-title":"Curr. Opin. Immunol."},{"key":"nanoad5f33bib47","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s13046-018-0777-4","article-title":"Immune checkpoint therapy in liver cancer","volume":"37","author":"Xu","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"nanoad5f33bib48","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13045-018-0582-8","article-title":"Next generation of immune checkpoint therapy in cancer: new developments and challenges","volume":"11","author":"Marin-Acevedo","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"nanoad5f33bib49","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/ijc.32181","article-title":"GITR ligation enhances functionality of tumor-infiltrating T cells in hepatocellular carcinoma","volume":"145","author":"van Beek","year":"2019","journal-title":"Int. J. Cancer"},{"key":"nanoad5f33bib50","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1053\/j.gastro.2017.06.017","article-title":"Antibodies against immune checkpoint molecules restore functions of tumor-infiltrating T cells in hepatocellular carcinomas","volume":"153","author":"Zhou","year":"2017","journal-title":"Gastroenterology"},{"key":"nanoad5f33bib51","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.canlet.2019.12.002","article-title":"Immunotherapy for hepatocellular carcinoma","volume":"470","author":"Zongyi","year":"2020","journal-title":"Cancer Lett."},{"key":"nanoad5f33bib52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.642958","article-title":"Tumor-intrinsic mechanisms regulating immune exclusion in liver cancers","volume":"12","author":"Lindblad","year":"2021","journal-title":"Front. Immunol."},{"key":"nanoad5f33bib53","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1200\/JCO.19.01307","article-title":"Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase iii trial","volume":"38","author":"Finn","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"nanoad5f33bib54","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1080\/13543784.2021.1940948","article-title":"Potential experimental immune checkpoint inhibitors for the treatment of cancer of the liver","volume":"30","author":"Hewitt","year":"2021","journal-title":"Expert Opin. Invest. Drugs"},{"key":"nanoad5f33bib55","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1200\/JCO.20.03555","article-title":"Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I\/II study","volume":"39","author":"Kelley","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"nanoad5f33bib56","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13354","article-title":"Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy","volume":"7","author":"Lee","year":"2016","journal-title":"Nat. Commun."},{"key":"nanoad5f33bib57","doi-asserted-by":"publisher","first-page":"252","DOI":"10.3389\/fimmu.2018.00252","article-title":"Clinical grade regulatory CD4(+) T cells (tregs): moving toward cellular-based immunomodulatory therapies","volume":"9","author":"Duggleby","year":"2018","journal-title":"Front. Immunol."},{"key":"nanoad5f33bib58","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.coi.2019.10.002","article-title":"New insights on T-cell self-tolerance","volume":"63","author":"Yi","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"nanoad5f33bib59","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1002\/hep.24149","article-title":"Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma","volume":"53","author":"Mizukoshi","year":"2011","journal-title":"Hepatology"},{"key":"nanoad5f33bib60","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.prp.2016.12.008","article-title":"Tumor-derived CD4+CD25+regulatory T cells inhibit dendritic cells function by CTLA-4","volume":"213","author":"Chen","year":"2017","journal-title":"Pathol. Res. Pract."},{"key":"nanoad5f33bib61","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jhep.2013.02.022","article-title":"A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C","volume":"59","author":"Sangro","year":"2013","journal-title":"J. Hepatol."},{"key":"nanoad5f33bib62","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.4564","article-title":"Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the checkmate 040 randomized clinical trial","volume":"6","author":"Yau","year":"2020","journal-title":"JAMA Oncol."},{"key":"nanoad5f33bib63","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.jhep.2016.10.029","article-title":"Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma","volume":"66","author":"Duffy","year":"2017","journal-title":"J. Hepatol."},{"key":"nanoad5f33bib64","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1186\/s12885-021-08033-x","article-title":"PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma","volume":"21","author":"Pinato","year":"2021","journal-title":"BMC Cancer"},{"key":"nanoad5f33bib65","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/bs.acr.2019.03.003","article-title":"Co-stimulatory and co-inhibitory pathways in cancer immunotherapy","volume":"143","author":"O\u2019Neill","year":"2019","journal-title":"Adv. Cancer Res."},{"key":"nanoad5f33bib66","doi-asserted-by":"publisher","first-page":"795","DOI":"10.4252\/wjsc.v13.i7.795","article-title":"Immunotherapy against programmed death-1\/programmed death ligand 1 in hepatocellular carcinoma: importance of molecular variations, cellular heterogeneity, and cancer stem cells","volume":"13","author":"Sukowati","year":"2021","journal-title":"World J. Stem Cells"},{"key":"nanoad5f33bib67","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1002\/ijc.25397","article-title":"PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients","volume":"128","author":"Shi","year":"2011","journal-title":"Int. J. Cancer"},{"key":"nanoad5f33bib68","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.immuni.2007.05.016","article-title":"Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses","volume":"27","author":"Butte","year":"2007","journal-title":"Immunity"},{"key":"nanoad5f33bib69","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1016\/S0140-6736(17)31046-2","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1\/2 dose escalation and expansion trial","volume":"389","author":"El-Khoueiry","year":"2017","journal-title":"Lancet"},{"key":"nanoad5f33bib70","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/S1470-2045(18)30351-6","article-title":"Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial","volume":"19","author":"Zhu","year":"2018","journal-title":"Lancet Oncol."},{"key":"nanoad5f33bib71","doi-asserted-by":"publisher","first-page":"v874","DOI":"10.1093\/annonc\/mdz394.029","article-title":"LBA38_PR\u2014CheckMate 459: a randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC)","volume":"30","author":"Yau","year":"2019","journal-title":"Ann. Oncol."},{"key":"nanoad5f33bib72","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1158\/1078-0432.CCR-21-3807","article-title":"Pembrolizumab monotherapy for previously untreated advanced hepatocellular carcinoma: data from the open-label, phase 2 KEYNOTE-224 trial","volume":"28","author":"Verset","year":"2022","journal-title":"Clin. Cancer. Res."},{"key":"nanoad5f33bib73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejca.2022.02.009","article-title":"Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib","volume":"167","author":"Kudo","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"nanoad5f33bib74","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1007\/s10637-022-01248-0","article-title":"Lenvatinib combined with nivolumab in advanced hepatocellular carcinoma-real-world experience","volume":"40","author":"Wu","year":"2022","journal-title":"Invest. New Drugs"},{"key":"nanoad5f33bib75","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/s41423-022-00848-3","article-title":"The combination of PD-1 blockade with interferon-\u03b1 has a synergistic effect on hepatocellular carcinoma","volume":"19","author":"Zhu","year":"2022","journal-title":"Cell Mol. Immunol."},{"key":"nanoad5f33bib76","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1182\/blood-2003-01-0273","article-title":"MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223)","volume":"102","author":"Andreae","year":"2003","journal-title":"Blood"},{"key":"nanoad5f33bib77","doi-asserted-by":"publisher","first-page":"3383","DOI":"10.1172\/JCI31184","article-title":"LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems","volume":"117","author":"Grosso","year":"2007","journal-title":"J. Clin. Invest."},{"key":"nanoad5f33bib78","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1084\/jem.171.5.1393","article-title":"LAG-3, a novel lymphocyte activation gene closely related to CD4","volume":"171","author":"Triebel","year":"1990","journal-title":"J. Exp. Med."},{"key":"nanoad5f33bib79","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1186\/s12967-020-02469-8","article-title":"Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8(+)T cells in hepatocellular carcinoma using multiplex quantitative analysis","volume":"18","author":"Guo","year":"2020","journal-title":"J. Transl. Med."},{"key":"nanoad5f33bib80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.754961","article-title":"Serum LAG-3 predicts outcome and treatment response in hepatocellular carcinoma patients with transarterial chemoembolization","volume":"12","author":"Guo","year":"2021","journal-title":"Front. Immunol."},{"key":"nanoad5f33bib81","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1016\/j.prp.2018.07.019","article-title":"Evaluation of the effect of TIM-3 suppression by miR-498 and its effect on apoptosis and proliferation rate of HL-60 cell line","volume":"214","author":"Moghaddam","year":"2018","journal-title":"Pathol. Res. Pract."},{"key":"nanoad5f33bib82","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1136\/gutjnl-2014-307671","article-title":"Tim-3 fosters HCC development by enhancing TGF-\u03b2-mediated alternative activation of macrophages","volume":"64","author":"Yan","year":"2015","journal-title":"Gut"},{"key":"nanoad5f33bib83","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.601661","article-title":"The role of TIM-3 in hepatocellular carcinoma: a promising target for immunotherapy?","volume":"10","author":"Ganjalikhani Hakemi","year":"2020","journal-title":"Front. Oncol."},{"key":"nanoad5f33bib84","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1021\/acs.nanolett.1c04977","article-title":"Neoantigen immunotherapeutic-gel combined with TIM-3 blockade effectively restrains orthotopic hepatocellular carcinoma progression","volume":"22","author":"Zhao","year":"2022","journal-title":"Nano Lett."},{"key":"nanoad5f33bib85","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.jcmgh.2021.03.003","article-title":"TIGIT and PD1 co-blockade restores ex vivo functions of human tumor-infiltrating CD8(+) T cells in hepatocellular carcinoma","volume":"12","author":"Ge","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"nanoad5f33bib86","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/s41467-018-08096-8","article-title":"Breakdown of adaptive immunotolerance induces hepatocellular carcinoma in HBsAg-tg mice","volume":"10","author":"Zong","year":"2019","journal-title":"Nat. Commun."},{"key":"nanoad5f33bib87","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.annonc.2021.11.002","article-title":"First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer(\u2606)","volume":"33","author":"Niu","year":"2022","journal-title":"Ann. Oncol."},{"key":"nanoad5f33bib88","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1158\/1078-0432.CCR-21-2780","article-title":"A phase 1a\/b open-label, dose-escalation study of etigilimab alone or in combination with nivolumab in patients with locally advanced or metastatic solid tumors","volume":"28","author":"Mettu","year":"2022","journal-title":"Clin. Cancer. Res."},{"key":"nanoad5f33bib89","doi-asserted-by":"publisher","first-page":"e1286","DOI":"10.1002\/cti2.1286","article-title":"Exploiting the CRISPR-Cas9 gene-editing system for human cancers and immunotherapy","volume":"10","author":"Afolabi","year":"2021","journal-title":"Clin. Transl. Immunol."},{"key":"nanoad5f33bib90","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.704999","article-title":"The application of CRISPR\/Cas9 technology for cancer immunotherapy: current status and problems","volume":"11","author":"Wang","year":"2021","journal-title":"Front. Oncol."},{"key":"nanoad5f33bib91","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202206399","article-title":"Silk-gel powered adenoviral vector enables robust genome editing of PD-L1 to augment immunotherapy across multiple tumor models","volume":"10","author":"Wu","year":"2023","journal-title":"Adv. Sci."},{"key":"nanoad5f33bib92","doi-asserted-by":"publisher","first-page":"5357","DOI":"10.1016\/j.cell.2021.09.006","article-title":"In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target","volume":"184","author":"Wang","year":"2021","journal-title":"Cell"},{"key":"nanoad5f33bib93","doi-asserted-by":"publisher","DOI":"10.1038\/srep20070","article-title":"CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients","volume":"6","author":"Su","year":"2016","journal-title":"Sci. Rep."},{"key":"nanoad5f33bib94","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/s41591-020-0840-5","article-title":"Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer","volume":"26","author":"Lu","year":"2020","journal-title":"Nat. Med."},{"key":"nanoad5f33bib95","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.gene.2017.09.010","article-title":"CRISPR knock out CTLA-4 enhances the anti-tumor activity of cytotoxic T lymphocytes","volume":"636","author":"Shi","year":"2017","journal-title":"Gene"},{"key":"nanoad5f33bib96","doi-asserted-by":"publisher","first-page":"5549","DOI":"10.1038\/s41598-018-23803-7","article-title":"Genetic abrogation of immune checkpoints in antigen-specific cytotoxic T-lymphocyte as a potential alternative to blockade immunotherapy","volume":"8","author":"Zhang","year":"2018","journal-title":"Sci. Rep."},{"key":"nanoad5f33bib97","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2022.2081415","article-title":"CRISPR-Cas9 based gene editing of the immune checkpoint NKG2A enhances NK cell mediated cytotoxicity against multiple myeloma","volume":"11","author":"Bexte","year":"2022","journal-title":"Oncoimmunology"},{"key":"nanoad5f33bib98","doi-asserted-by":"publisher","first-page":"3489","DOI":"10.3390\/ijms22073489","article-title":"CRISPR-Cas9-mediated TIM3 knockout in human natural killer cells enhances growth inhibitory effects on human glioma cells","volume":"22","author":"Morimoto","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"nanoad5f33bib99","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1039\/D1TB02688G","article-title":"Genome editing of PD-L1 mediated by nucleobase-modified polyamidoamine for cancer immunotherapy","volume":"10","author":"Wei","year":"2022","journal-title":"J. Mater. Chem. B"},{"key":"nanoad5f33bib100","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s12951-022-01304-0","article-title":"Therapeutic nucleus-access BNCT drug combined CD47-targeting gene editing in glioblastoma","volume":"20","author":"Chen","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"nanoad5f33bib101","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-01572-0","article-title":"HLA-G gene editing in tumor cell lines as a novel alternative in cancer immunotherapy","volume":"11","author":"Palma","year":"2021","journal-title":"Sci. Rep."},{"key":"nanoad5f33bib102","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.trsl.2020.11.005","article-title":"Loss of HCRP1 leads to upregulation of PD-L1 via STAT3 activation and is of prognostic significance in EGFR-dependent cancer","volume":"230","author":"Tomasich","year":"2021","journal-title":"Transl. Res."},{"key":"nanoad5f33bib103","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.apsb.2019.07.004","article-title":"Cdk5 knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity","volume":"10","author":"Deng","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"nanoad5f33bib104","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s11658-020-00233-w","article-title":"The MDM2 ligand Nutlin-3 differentially alters expression of the immune blockade receptors PD-L1 and CD276","volume":"25","author":"Li","year":"2020","journal-title":"Cell. Mol. Biol. Lett."},{"key":"nanoad5f33bib105","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1158\/2159-8290.CD-19-1448","article-title":"CRISPR-GEMM pooled mutagenic screening identifies KMT2D as a major modulator of immune checkpoint blockade","volume":"10","author":"Wang","year":"2020","journal-title":"Cancer Discov."},{"key":"nanoad5f33bib106","doi-asserted-by":"publisher","first-page":"3431","DOI":"10.1158\/1078-0432.CCR-19-1627","article-title":"Generation of genetically engineered mouse lung organoid models for squamous cell lung cancers allows for the study of combinatorial immunotherapy","volume":"26","author":"Hai","year":"2020","journal-title":"Clin. Cancer. Res."},{"key":"nanoad5f33bib107","doi-asserted-by":"publisher","first-page":"448","DOI":"10.3389\/fonc.2020.00448","article-title":"CRISPR\/Cas9-mediated Foxp1 silencing restores immune surveillance in an immunocompetent A20 lymphoma model","volume":"10","author":"Felce","year":"2020","journal-title":"Front. Oncol."},{"key":"nanoad5f33bib108","doi-asserted-by":"publisher","first-page":"eabl8247","DOI":"10.1126\/sciadv.abl8247","article-title":"In vivo multidimensional CRISPR screens identify Lgals2 as an immunotherapy target in triple-negative breast cancer","volume":"8","author":"Ji","year":"2022","journal-title":"Sci. Adv."},{"key":"nanoad5f33bib109","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.3390\/cells10071680","article-title":"Myostatin deficiency protects C2C12 cells from oxidative stress by inhibiting intrinsic activation of apoptosis","volume":"10","author":"Drysch","year":"2021","journal-title":"Cells"},{"key":"nanoad5f33bib110","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41420-021-00747-y","article-title":"Genome-scale CRISPR-Cas9 knockout screening in hepatocellular carcinoma with lenvatinib resistance","volume":"7","author":"Lu","year":"2021","journal-title":"Cell Death Discov."},{"key":"nanoad5f33bib111","doi-asserted-by":"publisher","first-page":"eabj4008","DOI":"10.1126\/science.abj4008","article-title":"CRISPR activation and interference screens decode stimulation responses in primary human T cells","volume":"375","author":"Schmidt","year":"2022","journal-title":"Science"},{"key":"nanoad5f33bib112","doi-asserted-by":"publisher","first-page":"3432","DOI":"10.1158\/1078-0432.CCR-20-3365","article-title":"Mutations in the IFN\u03b3-JAK-STAT pathway causing resistance to immune checkpoint inhibitors in melanoma increase sensitivity to oncolytic virus treatment","volume":"27","author":"Nguyen","year":"2021","journal-title":"Clin. Cancer. Res."},{"key":"nanoad5f33bib113","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1111\/imm.13094","article-title":"Genetic reprogramming for NK cell cancer immunotherapy with CRISPR\/Cas9","volume":"158","author":"Afolabi","year":"2019","journal-title":"Immunology"},{"key":"nanoad5f33bib114","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101009","article-title":"Synergistic effects of combined immunotherapy strategies in a model of multifocal hepatocellular carcinoma","volume":"4","author":"Ochoa","year":"2023","journal-title":"Cell Rep. Med."},{"key":"nanoad5f33bib115","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.jhep.2022.10.037","article-title":"Using mouse liver cancer models based on somatic genome editing to predict immune checkpoint inhibitor responses","volume":"78","author":"Yuen","year":"2023","journal-title":"J. Hepatol."},{"key":"nanoad5f33bib116","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.848327","article-title":"Effect of CRISPR\/Cas9-Edited PD-1\/PD-L1 on tumor immunity and immunotherapy","volume":"13","author":"Xu","year":"2022","journal-title":"Front. Immunol."},{"key":"nanoad5f33bib117","doi-asserted-by":"publisher","first-page":"3050","DOI":"10.1200\/JCO.2018.36.15_suppl.3050","article-title":"A phase I trial of PD-1 deficient engineered T cells with CRISPR\/Cas9 in patients with advanced non-small cell lung cancer","volume":"36","author":"Lu","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"nanoad5f33bib118","doi-asserted-by":"publisher","first-page":"4573","DOI":"10.12659\/MSM.910903","article-title":"Programmed death receptor 1 (PD1) knockout and human telomerase reverse transcriptase (hTERT) transduction can enhance persistence and antitumor efficacy of cytokine-induced killer cells against hepatocellular carcinoma","volume":"24","author":"Huang","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"nanoad5f33bib119","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.3389\/fphar.2018.01118","article-title":"Disruption of PD-1 enhanced the anti-tumor activity of chimeric antigen receptor T cells against hepatocellular carcinoma","volume":"9","author":"Guo","year":"2018","journal-title":"Front. Pharmacol."},{"key":"nanoad5f33bib120","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1136\/gutjnl-2017-314032","article-title":"Hepatoma-intrinsic CCRK inhibition diminishes myeloid-derived suppressor cell immunosuppression and enhances immune-checkpoint blockade efficacy","volume":"67","author":"Zhou","year":"2018","journal-title":"Gut"},{"key":"nanoad5f33bib121","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9965099","article-title":"KDM1A promotes immunosuppression in hepatocellular carcinoma by regulating PD-L1 through demethylating MEF2D","volume":"2021","author":"Wang","year":"2021","journal-title":"J. Immunol. Res."},{"key":"nanoad5f33bib122","doi-asserted-by":"publisher","first-page":"4176","DOI":"10.7150\/ijbs.67379","article-title":"Cullin3 deficiency shapes tumor microenvironment and promotes cholangiocarcinoma in liver-specific Smad4\/Pten mutant mice","volume":"17","author":"Zhao","year":"2021","journal-title":"Int. J. Bio. Sci."},{"key":"nanoad5f33bib123","doi-asserted-by":"publisher","first-page":"113","DOI":"10.2217\/imt-2020-0062","article-title":"Killing efficiency affected by mutually modulated PD-1 and PD-L1 expression via NKT-hepatoma cell interactions","volume":"13","author":"Liu","year":"2021","journal-title":"Immunotherapy"},{"key":"nanoad5f33bib124","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1038\/s41467-021-21804-1","article-title":"Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma","volume":"12","author":"Hung","year":"2021","journal-title":"Nat. Commun."},{"key":"nanoad5f33bib125","doi-asserted-by":"publisher","first-page":"5208","DOI":"10.18632\/oncotarget.23730","article-title":"CRISPR knock out of programmed cell death protein 1 enhances anti-tumor activity of cytotoxic T lymphocytes","volume":"9","author":"Zhao","year":"2018","journal-title":"Oncotarget"},{"key":"nanoad5f33bib126","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1007\/s00280-019-03800-x","article-title":"Disruption of CTLA-4 expression on peripheral blood CD8\u2009+\u2009T cell enhances anti-tumor efficacy in bladder cancer","volume":"83","author":"Zhang","year":"2019","journal-title":"Cancer Chemother. Pharmacol."},{"key":"nanoad5f33bib127","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1007\/s11684-017-0543-6","article-title":"CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells","volume":"11","author":"Zhang","year":"2017","journal-title":"Front. Med."},{"key":"nanoad5f33bib128","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.3390\/ijms23063207","article-title":"Simultaneous genetic ablation of PD-1, LAG-3, and TIM-3 in CD8 T cells delays tumor growth and improves survival outcome","volume":"23","author":"Ciraolo","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"nanoad5f33bib129","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1053\/j.gastro.2020.03.074","article-title":"Hepatocellular carcinoma cells up-regulate PVRL1, stabilizing PVR and inhibiting the cytotoxic T-cell response via TIGIT to mediate tumor resistance to PD1 inhibitors in mice","volume":"159","author":"Chiu","year":"2020","journal-title":"Gastroenterology"},{"key":"nanoad5f33bib130","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202207512","article-title":"CRISPR\/Cas9 genome editing for tissue-specific in vivo targeting: nanomaterials and translational perspective","volume":"10","author":"Sahel","year":"2023","journal-title":"Adv. Sci."},{"key":"nanoad5f33bib131","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.jconrel.2022.01.013","article-title":"Delivery of CRISPR-Cas tools for in vivo genome editing therapy: trends and challenges","volume":"342","author":"Taha","year":"2022","journal-title":"J. Control. Release."},{"key":"nanoad5f33bib132","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1002\/cac2.12366","article-title":"Current updates of CRISPR\/Cas9-mediated genome editing and targeting within tumor cells: an innovative strategy of cancer management","volume":"42","author":"Allemailem","year":"2022","journal-title":"Cancer Commun."},{"key":"nanoad5f33bib133","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1016\/j.apsb.2021.05.020","article-title":"In vivo delivery of CRISPR-Cas9 therapeutics: progress and challenges","volume":"B 11","author":"Behr","year":"2021","journal-title":"Acta Pharm. Sin."},{"key":"nanoad5f33bib134","doi-asserted-by":"publisher","first-page":"6088","DOI":"10.7150\/thno.72509","article-title":"Self-assembled traditional Chinese nanomedicine modulating tumor immunosuppressive microenvironment for colorectal cancer immunotherapy","volume":"12","author":"Mao","year":"2022","journal-title":"Theranostics"},{"key":"nanoad5f33bib135","doi-asserted-by":"publisher","first-page":"16018","DOI":"10.1021\/acsami.9b23084","article-title":"Reshaping tumor immune microenvironment through acidity-responsive nanoparticles featured with CRISPR\/Cas9-mediated programmed death-ligand 1 attenuation and chemotherapeutics-induced immunogenic cell death","volume":"12","author":"Tu","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"nanoad5f33bib136","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s13238-022-00906-6","article-title":"Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer","volume":"13","author":"Feng","year":"2022","journal-title":"Protein Cell"},{"key":"nanoad5f33bib137","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-96167-0","article-title":"Intrinsic activation of \u03b2-catenin signaling by CRISPR\/Cas9-mediated exon skipping contributes to immune evasion in hepatocellular carcinoma","volume":"11","author":"Akasu","year":"2021","journal-title":"Sci. Rep."},{"key":"nanoad5f33bib138","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.109806","article-title":"Inhibition of histone demethylase KDM4 by ML324 induces apoptosis through the unfolded protein response and Bim upregulation in hepatocellular carcinoma cells","volume":"353","author":"Kim","year":"2022","journal-title":"Chem. Biol. Interact."},{"key":"nanoad5f33bib139","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/nature.2016.20988","article-title":"CRISPR gene-editing tested in a person for the first time","volume":"539","author":"Cyranoski","year":"2016","journal-title":"Nature"},{"key":"nanoad5f33bib140","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/j.tplants.2019.09.006","article-title":"CRISPR\/cas system: recent advances and future prospects for genome editing","volume":"24","author":"Manghwar","year":"2019","journal-title":"Trends Plant Sci."},{"key":"nanoad5f33bib141","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.tips.2021.10.012","article-title":"CRISPR-based therapeutics: current challenges and future applications","volume":"43","author":"Modell","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"nanoad5f33bib142","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.exphem.2022.03.002","article-title":"CRISPR-Cas9 gene editing induced complex on-target outcomes in human cells","volume":"110","author":"Wen","year":"2022","journal-title":"Exp. Hematol."},{"key":"nanoad5f33bib143","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1038\/s41467-022-30228-4","article-title":"Genome editing in animals with minimal PAM CRISPR-Cas9 enzymes","volume":"13","author":"Vicencio","year":"2022","journal-title":"Nat. Commun."},{"key":"nanoad5f33bib144","doi-asserted-by":"publisher","first-page":"5899","DOI":"10.1111\/febs.16457","article-title":"Expanding PAM recognition and enhancing base editing activity of Cas9 variants with non-PI domain mutations derived from xCas9","volume":"289","author":"Xie","year":"2022","journal-title":"FEBS J."},{"key":"nanoad5f33bib145","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41591-018-0326-x","article-title":"Identification of preexisting adaptive immunity to Cas9 proteins in humans","volume":"25","author":"Charlesworth","year":"2019","journal-title":"Nat. Med."},{"key":"nanoad5f33bib146","doi-asserted-by":"publisher","first-page":"3497","DOI":"10.1038\/s41467-018-05843-9","article-title":"Cas9 immunity creates challenges for CRISPR gene editing therapies","volume":"9","author":"Crudele","year":"2018","journal-title":"Nat. Commun."},{"key":"nanoad5f33bib147","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12943-021-01487-4","article-title":"Strategies to overcome the main challenges of the use of CRISPR\/Cas9 as a replacement for cancer therapy","volume":"21","author":"Rasul","year":"2022","journal-title":"Mol. Cancer"},{"key":"nanoad5f33bib148","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.molmed.2015.05.006","article-title":"Germline genome-editing research and its socioethical implications","volume":"21","author":"Ishii","year":"2015","journal-title":"Trends Mol. Med."},{"key":"nanoad5f33bib149","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.jconrel.2023.08.028","article-title":"CRISPR\/Cas9-based application for cancer therapy: challenges and solutions for non-viral delivery","volume":"361","author":"Lin","year":"2023","journal-title":"J. Control. Release."},{"key":"nanoad5f33bib150","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12951-021-01201-y","article-title":"Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms","volume":"20","author":"Wang","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"nanoad5f33bib151","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.jconrel.2022.09.046","article-title":"Brain-targeted CRISPR\/Cas9 nanomedicine for effective glioblastoma therapy","volume":"351","author":"Ruan","year":"2022","journal-title":"J. Control. Release"},{"key":"nanoad5f33bib152","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1038\/nbt.3404","article-title":"Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition","volume":"33","author":"Kleinstiver","year":"2015","journal-title":"Nat. Biotechnol."}],"container-title":["Nanotechnology"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad5f33","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad5f33\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad5f33","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad5f33\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad5f33\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad5f33\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad5f33\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad5f33\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T14:55:25Z","timestamp":1749912925000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad5f33"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,17]]},"references-count":152,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2024,7,17]]},"published-print":{"date-parts":[[2024,9,30]]}},"URL":"https:\/\/doi.org\/10.1088\/1361-6528\/ad5f33","relation":{},"ISSN":["0957-4484","1361-6528"],"issn-type":[{"value":"0957-4484","type":"print"},{"value":"1361-6528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,17]]},"assertion":[{"value":"Current application and future perspective of CRISPR\/cas9 gene editing system mediated immune checkpoint for liver cancer treatment","name":"article_title","label":"Article Title"},{"value":"Nanotechnology","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2023-10-30","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-07-04","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-07-17","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}