{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T09:45:17Z","timestamp":1775123117644,"version":"3.50.1"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Chromatography B"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1016\/j.jchromb.2022.123149","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T10:13:05Z","timestamp":1643796785000},"page":"123149","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Pinpoint modification strategy for stabilization of single guide RNA"],"prefix":"10.1016","volume":"1192","author":[{"given":"Shoko","family":"Takeuchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuo","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eriya","family":"Kenjo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Karashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiro","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.jchromb.2022.123149_b0005","doi-asserted-by":"crossref","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."},{"issue":"6121","key":"10.1016\/j.jchromb.2022.123149_b0010","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science."},{"issue":"6121","key":"10.1016\/j.jchromb.2022.123149_b0015","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.1232033","article-title":"RNA-guided human genome engineering via Cas9","volume":"339","author":"Mali","year":"2013","journal-title":"Science."},{"key":"10.1016\/j.jchromb.2022.123149_b0020","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.00471","article-title":"RNA-programmed genome editing in human cells","volume":"2","author":"Jinek","year":"2013","journal-title":"Elife."},{"issue":"1","key":"10.1016\/j.jchromb.2022.123149_b0025","article-title":"CRISPR\/Cas9 - An evolving biological tool kit for cancer biology and oncology","volume":"3","author":"Tian","year":"2019","journal-title":"NPJ Precis. Oncol."},{"issue":"2","key":"10.1016\/j.jchromb.2022.123149_b0030","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s40291-019-00392-3","article-title":"Rare Opportunities: CRISPR\/Cas-based therapy development for rare genetic diseases","volume":"23","author":"Papasavva","year":"2019","journal-title":"Mol. Diagnosis Ther."},{"key":"10.1016\/j.jchromb.2022.123149_b0035","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.omtm.2019.02.008","article-title":"Advancements and obstacles of CRISPR-Cas9 technology in translational research","volume":"13","author":"You","year":"2019","journal-title":"Mol. Ther. Methods. Clin. Dev."},{"key":"10.1016\/j.jchromb.2022.123149_b0040","doi-asserted-by":"crossref","first-page":"e264","DOI":"10.1038\/mtna.2015.37","article-title":"Off-target effects in CRISPR\/Cas9-mediated genome engineering","volume":"4","author":"Zhang","year":"2015","journal-title":"Mol. Ther. Nucleic Acids."},{"issue":"15","key":"10.1016\/j.jchromb.2022.123149_b0045","doi-asserted-by":"crossref","first-page":"9874","DOI":"10.1021\/acs.chemrev.6b00799","article-title":"CRISPR\/Cas9-based genome editing for disease modeling and therapy: Challenges and opportunities for nonviral delivery","volume":"117","author":"Wang","year":"2017","journal-title":"Chem. Rev."},{"key":"10.1016\/j.jchromb.2022.123149_b0050","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1242\/jcs.066399","article-title":"Breaking down the barriers: siRNA delivery and endosome escape","volume":"123","author":"Dominska","year":"2010","journal-title":"J. Cell Sci."},{"issue":"3","key":"10.1016\/j.jchromb.2022.123149_b0055","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nbt.3802","article-title":"Overcoming cellular barriers for RNA therapeutics","volume":"35","author":"Dowdy","year":"2017","journal-title":"Nat. Biotechnol."},{"issue":"2","key":"10.1016\/j.jchromb.2022.123149_b0060","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/nrd2742","article-title":"Knocking down barriers: advances in siRNA delivery","volume":"8","author":"Whitehead","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"issue":"19-20","key":"10.1016\/j.jchromb.2022.123149_b0065","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.drudis.2008.05.007","article-title":"Chemically modified siRNA: tools and applications","volume":"13","author":"Watts","year":"2008","journal-title":"Drug Discov Today."},{"key":"10.1016\/j.jchromb.2022.123149_b0070","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1093\/nar\/gky037","article-title":"Comparison of partially and fully chemically-modified siRNA in conjugate-mediated delivery in vivo","volume":"46","author":"Hassler","year":"2018","journal-title":"Nucleic Acids Res."},{"issue":"9","key":"10.1016\/j.jchromb.2022.123149_b0075","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/nbt.3290","article-title":"Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells","volume":"33","author":"Hendel","year":"2015","journal-title":"Nat. Biotechnol."},{"issue":"51","key":"10.1016\/j.jchromb.2022.123149_b0080","doi-asserted-by":"crossref","first-page":"E7110","DOI":"10.1073\/pnas.1520883112","article-title":"Synthetic CRISPR RNA-Cas9\u2013guided genome editing in human cells","volume":"112","author":"Rahdar","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jchromb.2022.123149_b0085","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1038\/s41467-018-05073-z","article-title":"Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing","volume":"9","author":"Mir","year":"2018","journal-title":"Nat. Commun."},{"issue":"12","key":"10.1016\/j.jchromb.2022.123149_b0090","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1038\/nbt.4005","article-title":"Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing","volume":"35","author":"Yin","year":"2017","journal-title":"Nat. Biotechnol."},{"issue":"9","key":"10.1016\/j.jchromb.2022.123149_b0095","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1016\/j.celrep.2018.02.014","article-title":"A single administration of CRISPR\/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing","volume":"22","author":"Finn","year":"2018","journal-title":"Cell rep."},{"issue":"3","key":"10.1016\/j.jchromb.2022.123149_b0100","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1158\/1535-7163.MCT-06-0195","article-title":"Evaluation of locked nucleic acid\u2013modified small interfering RNA in vitro and in vivo","volume":"6","author":"Mook","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.jchromb.2022.123149_b0105","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.omtn.2017.10.003","article-title":"Site-Specific modification using the 2\u2032-methoxyethyl group improves the specificity and activity of siRNAs","volume":"9","author":"Song","year":"2017","journal-title":"Mol. Ther. Nucleic Acids."},{"issue":"1","key":"10.1016\/j.jchromb.2022.123149_b0110","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1039\/B611612D","article-title":"MALDI-TOF mass spectral analysis of siRNA degradation in serum confirms an RNAse A-like activity","volume":"3","author":"Turner","year":"2007","journal-title":"Mol. Biosyst."},{"key":"10.1016\/j.jchromb.2022.123149_b0115","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/s41598-018-37642-z","article-title":"HPLC methods for purity evaluation of man-made single-stranded RNAs","volume":"9","author":"Kanavarioti","year":"2019","journal-title":"Sci. Rep."},{"issue":"44","key":"10.1016\/j.jchromb.2022.123149_b0120","doi-asserted-by":"crossref","first-page":"14792","DOI":"10.1021\/acs.analchem.1c03533","article-title":"Full Sequencing of CRISPR\/Cas9 Single Guide RNA (sgRNA) via Parallel Ribonuclease Digestions and Hydrophilic Interaction Liquid Chromatography\u2212High-Resolution Mass Spectrometry Analysis","volume":"93","author":"Goyon","year":"2021","journal-title":"Anal. Chem."},{"issue":"2","key":"10.1016\/j.jchromb.2022.123149_b0125","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1021\/acs.analchem.1c04350","article-title":"On-line Sequencing of CRISPR Guide RNAs and Their Impurities via the Use of Immobilized Ribonuclease Cartridges Attached to a 2D\/3D-LC\u2212MS System","volume":"94","author":"Goyon","year":"2022","journal-title":"Anal. Chem."},{"issue":"6096","key":"10.1016\/j.jchromb.2022.123149_b0130","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA\u2013guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science."},{"issue":"1-2","key":"10.1016\/j.jchromb.2022.123149_b0135","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ijpharm.2010.12.010","article-title":"The application of MALDI TOF MS in biopharmaceutical research","volume":"417","author":"Kafka","year":"2011","journal-title":"Int. J. Pharm."},{"issue":"19","key":"10.1016\/j.jchromb.2022.123149_b0140","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1093\/nar\/22.19.3866","article-title":"Matrix assisted laser desorption\/ionization mass spectrometry of enzymatically synthesized RNA up to 150 kDa","volume":"22","author":"Kirpekar","year":"1994","journal-title":"Nucleic Acids Res."},{"issue":"5","key":"10.1016\/j.jchromb.2022.123149_b0145","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1021\/cr030040w","article-title":"Recent developments in mass spectrometry for the characterization of nucleosides, nucleotides, oligonucleotides, and nucleic acids","volume":"105","author":"Banoub","year":"2005","journal-title":"Chem. Rev."},{"key":"10.1016\/j.jchromb.2022.123149_b0150","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1038\/mtna.2011.4","article-title":"siRNA-optimized modifications for enhanced in vivo activity","volume":"1","author":"Kenski","year":"2012","journal-title":"Mol. Ther. Nucleic Acids."},{"issue":"9","key":"10.1016\/j.jchromb.2022.123149_b0155","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1261\/rna.5103703","article-title":"siRNA function in RNAi: A chemical modification analysis","volume":"9","author":"Chiu","year":"2003","journal-title":"RNA"},{"key":"10.1016\/j.jchromb.2022.123149_b0160","first-page":"546","article-title":"Extensive CRISPR RNA modification reveals chemical compatibility and structure-activity relationships for Cas9 biochemical activity","volume":"47","author":"O\u2019Reilly","year":"2019","journal-title":"Nucleic Acids Res."},{"issue":"10","key":"10.1016\/j.jchromb.2022.123149_b0165","doi-asserted-by":"crossref","first-page":"5633","DOI":"10.1073\/pnas.97.10.5633","article-title":"Potent and nontoxic antisense oligonucleotides containing locked nucleic acids","volume":"97","author":"Wahlestedt","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"3","key":"10.1016\/j.jchromb.2022.123149_b0170","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jbbm.2004.01.007","article-title":"Comparison of selected analytical techniques for protein sizing, quantitation and molecular weight determination","volume":"60","author":"Goetz","year":"2004","journal-title":"J. Biochem. Biophys. Methods."},{"issue":"9","key":"10.1016\/j.jchromb.2022.123149_b0175","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1093\/nar\/gkp106","article-title":"A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity","volume":"37","author":"Bramsen","year":"2009","journal-title":"Nucleic acids res."},{"key":"10.1016\/j.jchromb.2022.123149_b0180","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.1093\/nar\/gkh862","article-title":"Application of locked nucleic acids to improve aptamer in vivo stability and targeting function","volume":"32","author":"Schmidt","year":"2004","journal-title":"Nucleic Acids Res."},{"issue":"4","key":"10.1016\/j.jchromb.2022.123149_b0185","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1089\/oli.2008.0164","article-title":"Chemical modification of siRNAs for in vivo use","volume":"18","author":"Behlke","year":"2008","journal-title":"Oligonucleotides"}],"container-title":["Journal of Chromatography B"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1570023222000538?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1570023222000538?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T23:08:03Z","timestamp":1761606483000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1570023222000538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":37,"alternative-id":["S1570023222000538"],"URL":"https:\/\/doi.org\/10.1016\/j.jchromb.2022.123149","relation":{},"ISSN":["1570-0232"],"issn-type":[{"value":"1570-0232","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pinpoint modification strategy for stabilization of single guide RNA","name":"articletitle","label":"Article Title"},{"value":"Journal of Chromatography B","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jchromb.2022.123149","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"123149"}}