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Existing CRISPR\u2010based assays face two major limitations that restrict their application for sepsis: narrow protospacer adjacent motif (PAM) site compatibility and poor enzyme stability under clinical and environmental stresses. A modular diagnostic platform is presented, CRISPR\u2010FLEXMO (CRISPR with flexible PAM in metal\u2010organic framework encapsulation, MOF), which integrates a PAM\u2010relaxed Cas12a variant (K607R) with a manganese\u2010coordinated MOF (Mn\u2010MOF) for stable and specific detection of sepsis\u2010causing bacteria. The system targets a conserved region upstream of the Shine\u2010Dalgarno sequence in the 16S rRNA gene containing a universal TTCC PAM, enabling broad\u2010spectrum detection with a single universal primer pair across Gram\u2010negative and Gram\u2010positive pathogens. The K607R variant shows enhanced\n                    <jats:italic>cis<\/jats:italic>\n                    \u2010 and\n                    <jats:italic>trans<\/jats:italic>\n                    \u2010cleavage activity, while Mn\u2010MOF encapsulation maintains enzyme functionality under ambient, thermal, and chaotropic stress. The assay detects as low as 10 CFU\u00a0mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    in bacterial lysates following amplification and achieves 100% sensitivity and specificity in serum samples from 15 sepsis patients and 3 healthy individuals, with no cross\u2010reactivity to six respiratory viruses. The platform retains over 78% activity after 12 weeks of room\u2010temperature storage, offering a field\u2010deployable CRISPR diagnostic solution for next\u2010generation infectious disease detection.\n                  <\/jats:p>","DOI":"10.1002\/advs.202513439","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T05:24:26Z","timestamp":1763961866000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CRISPR in MOF Formulation with Enhanced Stability, Activity, and Altered PAM Specificity for Broad\u2010Spectrum Diagnosis of Bacterial Sepsis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-6974","authenticated-orcid":false,"given":"Tathagata","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of California  Riverside CA 92521 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9567-2902","authenticated-orcid":false,"given":"Zilong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of California  Riverside CA 92521 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1807-5161","authenticated-orcid":false,"given":"Meera G.","family":"Nair","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences School of Medicine University of California  Riverside CA 92521 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6484-2739","authenticated-orcid":false,"given":"Juhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of California  Riverside CA 92521 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,23]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201504-0781OC"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000217961.75225.E9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0884533617695243"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06506-y"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-019-2478-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703058"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431x20198595"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-021-00765-y"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)01044-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c05431"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0371-x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c03975"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c02372"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0210-2"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4LC00340C"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00760-7"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2022.114712"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2021.113732"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20633-y"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37200-w"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048558"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4AY00848K"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0958-1669(02)00328-2"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja513058h"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c18266"},{"key":"e_1_2_8_27_1","volume":"34","author":"Ma X.","year":"2024","journal-title":"Adv. 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