{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T07:21:23Z","timestamp":1783149683542,"version":"3.54.6"},"reference-count":114,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004366","name":"Tabriz University of Medical Sciences","doi-asserted-by":"publisher","award":["76148"],"award-info":[{"award-number":["76148"]}],"id":[{"id":"10.13039\/501100004366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004366","name":"Tabriz University of Medical Sciences","doi-asserted-by":"publisher","award":["IR.TBZMED.VCR.REC.1404.028"],"award-info":[{"award-number":["IR.TBZMED.VCR.REC.1404.028"]}],"id":[{"id":"10.13039\/501100004366","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biotechnology"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.jbiotec.2026.04.017","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T15:16:23Z","timestamp":1777734983000},"page":"125-137","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Synthetic biology-driven innovations in triple-negative breast cancer: Integrating engineering design with targeted therapeutics"],"prefix":"10.1016","volume":"416","author":[{"given":"Negar","family":"Saliani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Saeid","family":"Hejazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Zununi Vahed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elnaz","family":"Mehdizadeh Aghdam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikoo","family":"Hasheminejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Daroon Parvar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5010-7293","authenticated-orcid":false,"given":"Soheila","family":"Montazersaheb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-5073","authenticated-orcid":false,"given":"Vida","family":"Ebrahimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41523-022-00486-y","article-title":"Immunotherapy in triple negative breast cancer: beyond checkpoint inhibitors","volume":"8","author":"Abdou","year":"2022","journal-title":"NPJ Breast Cancer"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib2","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2024.1491282","article-title":"Combining the induced pluripotent stem cell (iPSC) technology with chimeric antigen receptor (CAR)-based immunotherapy: recent advances, challenges, and future prospects","volume":"12","author":"Alidadi","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"issue":"5","key":"10.1016\/j.jbiotec.2026.04.017_bib3","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2019102169","article-title":"situ CRISPR-Cas9 base editing for the development of genetically engineered mouse models of breast cancer","volume":"39","author":"Annunziato","year":"2020","journal-title":"EMBO J."},{"issue":"6","key":"10.1016\/j.jbiotec.2026.04.017_bib4","doi-asserted-by":"crossref","DOI":"10.1080\/21645515.2022.2114254","article-title":"Current updates on generations, approvals, and clinical trials of CAR T-cell therapy","volume":"18","author":"Asmamaw Dejenie","year":"2022","journal-title":"Hum. Vaccin. & Immunother."},{"issue":"6","key":"10.1016\/j.jbiotec.2026.04.017_bib5","doi-asserted-by":"crossref","first-page":"5867","DOI":"10.3390\/ijms24065867","article-title":"Estrogen receptor \u03b24 regulates chemotherapy resistance and induces cancer stem cells in triple negative breast cancer","volume":"24","author":"Bano","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2051-1426-2-25","article-title":"Multiple chimeric antigen receptors successfully target chondroitin sulfate proteoglycan 4 in several different cancer histologies and cancer stem cells","volume":"2","author":"Beard","year":"2014","journal-title":"J. Immunother. Cancer"},{"issue":"4","key":"10.1016\/j.jbiotec.2026.04.017_bib7","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1158\/0008-5472.CAN-21-0373","article-title":"Loss of integrin-linked kinase sensitizes breast cancer to SRC inhibitors","volume":"82","author":"Beetham","year":"2022","journal-title":"Cancer Res."},{"issue":"2","key":"10.1016\/j.jbiotec.2026.04.017_bib8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41571-021-00565-2","article-title":"Treatment landscape of triple-negative breast cancer\u2014expanded options, evolving needs","volume":"19","author":"Bianchini","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib9","doi-asserted-by":"crossref","unstructured":"Bonf\u00e1 G., Martino G., Sellitto A., Rinaldi A., Tedeschi F., Caliendo F., et al. Design of novel synthetic promoters to tune gene expression in T cells. bioRxiv. 2025:2025.01. 09.632034.","DOI":"10.1101\/2025.01.09.632034"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fbioe.2019.00043","article-title":"Engineered cell-based therapeutics: synthetic biology meets immunology","volume":"7","author":"Caliendo","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"issue":"12","key":"10.1016\/j.jbiotec.2026.04.017_bib11","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.jfma.2018.06.013","article-title":"Patient-derived induced pluripotent stem cells for models of cancer and cancer stem cell research","volume":"117","author":"Chao","year":"2018","journal-title":"J. Formos. Med. Assoc."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib12","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1038\/s41467-020-15508-1","article-title":"Developing a new class of engineered live bacterial therapeutics to treat human diseases","volume":"11","author":"Charbonneau","year":"2020","journal-title":"Nat. Commun."},{"issue":"17","key":"10.1016\/j.jbiotec.2026.04.017_bib13","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1158\/0008-5472.CAN-11-0103","article-title":"IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression","volume":"71","author":"Chmielewski","year":"2011","journal-title":"Cancer Res."},{"issue":"658","key":"10.1016\/j.jbiotec.2026.04.017_bib14","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.abb9820","article-title":"ELP-dependent expression of MCL1 promotes resistance to EGFR inhibition in triple-negative breast cancer cells","volume":"13","author":"Cruz-Gordillo","year":"2020","journal-title":"Sci. Signal."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib15","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1038\/s41467-021-23316-4","article-title":"vivo genome-wide CRISPR screen reveals breast cancer vulnerabilities and synergistic mTOR\/Hippo targeted combination therapy","volume":"12","author":"Dai","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib16","series-title":"Stem Cells and Good Manufacturing Practices: Methods, Protocols, and Regulations","first-page":"179","article-title":"Addressing manufacturing challenges for commercialization of iPSC-based therapies","author":"Dashtban","year":"2020"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib17","article-title":"Gated chimeric antigen receptor T-cells: the next logical step in reducing toxicity?","volume":"5","author":"Davies","year":"2016","journal-title":"Transl. Cancer Res."},{"issue":"12","key":"10.1016\/j.jbiotec.2026.04.017_bib18","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1158\/1535-7163.MCT-20-0385","article-title":"Emerging CAR-T cell therapy for the treatment of triple-negative breast cancer","volume":"19","author":"Dees","year":"2020","journal-title":"Mol. Cancer Ther."},{"issue":"18","key":"10.1016\/j.jbiotec.2026.04.017_bib19","doi-asserted-by":"crossref","first-page":"4353","DOI":"10.3390\/cancers14184353","article-title":"Targeting the heterogeneous genomic landscape in triple-negative breast cancer through inhibitors of the transcriptional machinery","volume":"14","author":"van der Noord","year":"2022","journal-title":"Cancers"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib20","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.1020121","article-title":"Understanding and harnessing triple-negative breast cancer-related microbiota in oncology","volume":"12","author":"Devoy","year":"2022","journal-title":"Front. Oncol."},{"issue":"8","key":"10.1016\/j.jbiotec.2026.04.017_bib21","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1093\/annonc\/mdx157","article-title":"BET inhibitors: a novel epigenetic approach","volume":"28","author":"Doroshow","year":"2017","journal-title":"Ann. Oncol."},{"issue":"5","key":"10.1016\/j.jbiotec.2026.04.017_bib22","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3390\/cells8050403","article-title":"Current challenges of iPSC-based disease modeling and therapeutic implications","volume":"8","author":"Doss","year":"2019","journal-title":"Cells"},{"issue":"12","key":"10.1016\/j.jbiotec.2026.04.017_bib23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0297-0","article-title":"Bacteria-cancer interactions: bacteria-based cancer therapy","volume":"51","author":"Duong","year":"2019","journal-title":"Exp. & Mol. Med."},{"issue":"15","key":"10.1016\/j.jbiotec.2026.04.017_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2021.06.014","article-title":"Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer","volume":"81","author":"Einstein","year":"2021","journal-title":"Mol. Cell"},{"issue":"35","key":"10.1016\/j.jbiotec.2026.04.017_bib25","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adn9857","article-title":"Multi-armored allogeneic MUC1 CAR T cells enhance efficacy and safety in triple-negative breast cancer","volume":"10","author":"Erler","year":"2024","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib26","first-page":"720","article-title":"Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors","volume":"90","author":"Eshhar","year":"1993"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib27","doi-asserted-by":"crossref","DOI":"10.1002\/nano.202400015","article-title":"Advances in breast cancer research using CRISPR\/Cas9 system","author":"Eskandari","year":"2024","journal-title":"Nano Sel."},{"issue":"7_ement","key":"10.1016\/j.jbiotec.2026.04.017_bib28","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1158\/1538-7445.AM2023-3203","article-title":"EVO cells Oncology: tailored genetic engineering of iPSC-derived immune effector cells and combination with the right biologic therapeutics result in optimal killing of primary tumor cells from patients","volume":"83","author":"Esquerr\u00e9","year":"2023","journal-title":"Cancer Res."},{"issue":"6","key":"10.1016\/j.jbiotec.2026.04.017_bib29","doi-asserted-by":"crossref","first-page":"504","DOI":"10.3390\/arm92060045","article-title":"Prospects for Treatment of Lung Cancer Using Activated Lymphocytes Combined with Other Anti-Cancer Modalities","volume":"92","author":"Ganina","year":"2024","journal-title":"Adv. Respir. Med."},{"issue":"4","key":"10.1016\/j.jbiotec.2026.04.017_bib30","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1158\/1078-0432.CCR-13-2218","article-title":"T lymphocytes redirected against the chondroitin sulfate proteoglycan-4 control the growth of multiple solid tumors both in vitro and in vivo","volume":"20","author":"Geldres","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib31","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2023.1158539","article-title":"Novel chimeric antigen receptor T cell-based immunotherapy: a perspective for triple-negative breast cancer","volume":"11","author":"Geng","year":"2023","journal-title":"Front. Cell Dev. Biol."},{"issue":"7","key":"10.1016\/j.jbiotec.2026.04.017_bib32","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1007\/s00432-022-04304-7","article-title":"CRISPR\/Cas9 mediated knocking out of OPN gene enhances radiosensitivity in MDA-MB-231 breast cancer cell line","volume":"149","author":"Ghanbarnasab Behbahani","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib33","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/s12964-024-01577-y","article-title":"CDK7 in breast cancer: mechanisms of action and therapeutic potential","volume":"22","author":"Gong","year":"2024","journal-title":"Cell Commun. Signal."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib34","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1186\/s12967-024-05554-4","article-title":"A systematic review of non-coding RNA therapeutics in early clinical trials: a new perspective against cancer","volume":"22","author":"Grillone","year":"2024","journal-title":"J. Transl. Med."},{"issue":"4","key":"10.1016\/j.jbiotec.2026.04.017_bib35","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1021\/acssynbio.1c00236","article-title":"Sense-and-respond payload delivery using a novel antigen-inducible promoter improves suboptimal CAR-T activation","volume":"11","author":"Guo","year":"2022","journal-title":"ACS Synth. Biol."},{"issue":"12","key":"10.1016\/j.jbiotec.2026.04.017_bib36","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.3390\/vaccines9121497","article-title":"Bacterial-based cancer therapy (BBCT): recent advances, current challenges, and future prospects for cancer immunotherapy","volume":"9","author":"Gupta","year":"2021","journal-title":"Vaccines"},{"issue":"5","key":"10.1016\/j.jbiotec.2026.04.017_bib37","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.3390\/microorganisms11051355","article-title":"Tryptophanase Expressed by Salmonella Halts Breast Cancer Cell Growth In Vitro and Inhibits Production of Immunosuppressive Kynurenine","volume":"11","author":"Hababag","year":"2023","journal-title":"Microorganisms"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.114609","article-title":"Advances in chimeric antigen receptor T cells therapy in the treatment of breast cancer","volume":"162","author":"He","year":"2023","journal-title":"Biomed. & Pharmacother."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib39","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00262-018-2281-2","article-title":"CRISPR\/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions","volume":"68","author":"Hu","year":"2019","journal-title":"Cancer Immunol. Immunother."},{"issue":"26","key":"10.1016\/j.jbiotec.2026.04.017_bib40","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abl8247","article-title":"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."},{"issue":"6382","key":"10.1016\/j.jbiotec.2026.04.017_bib41","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"issue":"3","key":"10.1016\/j.jbiotec.2026.04.017_bib42","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nm.4478","article-title":"A novel chimeric antigen receptor containing a JAK\u2013STAT signaling domain mediates superior antitumor effects","volume":"24","author":"Kagoya","year":"2018","journal-title":"Nat. Med."},{"issue":"9","key":"10.1016\/j.jbiotec.2026.04.017_bib43","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1021\/acs.jproteome.2c00332","article-title":"Glycoproteomics identifies plexin-B3 as a targetable cell surface protein required for the growth and invasion of triple-negative breast cancer cells","volume":"21","author":"Kuhlmann","year":"2022","journal-title":"J. Proteome Res."},{"issue":"10","key":"10.1016\/j.jbiotec.2026.04.017_bib44","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41568-021-00389-3","article-title":"Synthetic biomarkers: a twenty-first century path to early cancer detection","volume":"21","author":"Kwong","year":"2021","journal-title":"Nat. Rev. Cancer"},{"issue":"6","key":"10.1016\/j.jbiotec.2026.04.017_bib45","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.7150\/thno.70581","article-title":"Chemotherapy-induced adenosine A2B receptor expression mediates epigenetic regulation of pluripotency factors and promotes breast cancer stemness","volume":"12","author":"Lan","year":"2022","journal-title":"Theranostics"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib46","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2022-071674","article-title":"Advances in systemic therapies for triple negative breast cancer","volume":"381","author":"Leon-Ferre","year":"2023","journal-title":"Bmj"},{"issue":"5","key":"10.1016\/j.jbiotec.2026.04.017_bib47","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1109\/JPROC.2021.3134169","article-title":"Synthetic gene circuits: design, implement, and apply","volume":"110","author":"Lezia","year":"2021","journal-title":"Proc. IEEE"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib48","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12943-024-02023-w","article-title":"Regulatory mechanisms of PD-1\/PD-L1 in cancers","volume":"23","author":"Lin","year":"2024","journal-title":"Mol. Cancer"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib49","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1158\/0008-5472.CAN-20-2245","article-title":"Targeting CDK12 for cancer therapy: function, mechanism, and drug discovery","volume":"81","author":"Liu","year":"2021","journal-title":"Cancer Res."},{"issue":"23","key":"10.1016\/j.jbiotec.2026.04.017_bib50","doi-asserted-by":"crossref","first-page":"11054","DOI":"10.18632\/aging.102510","article-title":"EGFR-specific CAR-T cells trigger cell lysis in EGFR-positive TNBC","volume":"11","author":"Liu","year":"2019","journal-title":"Aging (Albany NY)"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib51","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12943-023-01850-7","article-title":"Advances in immunotherapy for triple-negative breast cancer","volume":"22","author":"Liu","year":"2023","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib52","series-title":"Mammalian Synthetic Promoters","first-page":"249","article-title":"Computational sequence design with R2oDNA designer","author":"MacDonald","year":"2017"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib53","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1158\/0008-5472.CAN-17-1636","article-title":"MUC1-C induces PD-L1 and immune evasion in triple-negative breast cancer","volume":"78","author":"Maeda","year":"2018","journal-title":"Cancer Res."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib54","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/nbt0102-70","article-title":"Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCR\u03b6\/CD28 receptor","volume":"20","author":"Maher","year":"2002","journal-title":"Nat. Biotechnol."},{"issue":"7","key":"10.1016\/j.jbiotec.2026.04.017_bib55","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s13238-021-00876-1","article-title":"Therapeutic cell engineering: designing programmable synthetic genetic circuits in mammalian cells","volume":"13","author":"Mansouri","year":"2022","journal-title":"Protein & Cell"},{"issue":"2","key":"10.1016\/j.jbiotec.2026.04.017_bib56","doi-asserted-by":"crossref","DOI":"10.1002\/btm2.10474","article-title":"Optimization of CRISPR\u2013Cas system for clinical cancer therapy","volume":"8","author":"Meng","year":"2023","journal-title":"Bioeng. & Transl. Med."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib57","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1188049","article-title":"From bench to bedside: the history and progress of CAR T cell therapy","volume":"14","author":"Mitra","year":"2023","journal-title":"Front. Immunol."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib58","doi-asserted-by":"crossref","DOI":"10.1002\/cmdc.202300359","article-title":"Recent Progress in Prompt Molecular Detection of Exosomes Using CRISPR\/Cas and Microfluidic-Assisted Approaches Toward Smart Cancer Diagnosis and Analysis","volume":"19","author":"Mojtaba Mousavi","year":"2024","journal-title":"ChemMedChem"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib59","doi-asserted-by":"crossref","DOI":"10.1016\/j.envres.2023.116573","article-title":"Advancement in precision diagnosis and therapeutic for triple-negative breast cancer: Harnessing diagnostic potential of CRISPR-cas & engineered CAR T-cells mediated therapeutics","volume":"235","author":"Nayak","year":"2023","journal-title":"Environ. Res."},{"issue":"6","key":"10.1016\/j.jbiotec.2026.04.017_bib60","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/cge.14424","article-title":"Prospects and challenges of CRISPR\/Cas9 gene-editing technology in cancer research","volume":"104","author":"Ning","year":"2023","journal-title":"Clin. Genet."},{"issue":"1-2","key":"10.1016\/j.jbiotec.2026.04.017_bib61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/hum.2023.29263.bfs","article-title":"CASGEVY makes history as FDA approves first CRISPR\/Cas9 genome edited therapy","volume":"35","author":"Philippidis","year":"2024","journal-title":"Hum. Gene Ther."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib62","doi-asserted-by":"crossref","first-page":"7160","DOI":"10.1038\/s41467-025-62529-9","article-title":"Computational identification of small molecules for increased gene expression by synthetic circuits in mammalian cells","volume":"16","author":"Pisani","year":"2025","journal-title":"Nat. Commun."},{"issue":"17","key":"10.1016\/j.jbiotec.2026.04.017_bib63","doi-asserted-by":"crossref","first-page":"4364","DOI":"10.3390\/cancers15174364","article-title":"Applications of CRISPR technology to breast cancer and triple negative breast cancer research","volume":"15","author":"Pont","year":"2023","journal-title":"Cancers"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib64","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12943-024-02029-4","article-title":"Genome-wide in vivo CRISPR screen identifies TGF\u03b23 as actionable biomarker of palbociclib resistance in triple negative breast cancer","volume":"23","author":"Poulet","year":"2024","journal-title":"Mol. Cancer"},{"issue":"5","key":"10.1016\/j.jbiotec.2026.04.017_bib65","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/s41588-023-01355-5","article-title":"Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer","volume":"55","author":"Ravi","year":"2023","journal-title":"Nat. Genet."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib66","article-title":"A general logic-gating framework for CAR-T and nanocarrier cancer therapies","author":"Rehorst","year":"2025","journal-title":"J. Control. Release"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib67","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40364-022-00371-7","article-title":"Nanobody-based CAR-T cells for cancer immunotherapy","volume":"10","author":"Safarzadeh Kozani","year":"2022","journal-title":"Biomark. Res."},{"issue":"4","key":"10.1016\/j.jbiotec.2026.04.017_bib68","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1158\/1078-0432.CCR-16-0943","article-title":"miR-206 inhibits stemness and metastasis of breast cancer by targeting MKL1\/IL11 pathway","volume":"23","author":"Samaeekia","year":"2017","journal-title":"Clin. Cancer Res."},{"issue":"5","key":"10.1016\/j.jbiotec.2026.04.017_bib69","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.3390\/cancers15051597","article-title":"The new frontier of immunotherapy: chimeric antigen receptor T (CAR-T) cell and macrophage (CAR-M) therapy against breast cancer","volume":"15","author":"Schepisi","year":"2023","journal-title":"Cancers"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib70","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41420-020-00383-y","article-title":"Single-cell long noncoding RNA (lncRNA) transcriptome implicates MALAT1 in triple-negative breast cancer (TNBC) resistance to neoadjuvant chemotherapy","volume":"7","author":"Shaath","year":"2021","journal-title":"Cell Death Discov."},{"issue":"8","key":"10.1016\/j.jbiotec.2026.04.017_bib71","doi-asserted-by":"crossref","first-page":"5278","DOI":"10.1021\/acs.analchem.9b00073","article-title":"High-fidelity and rapid quantification of miRNA combining crRNA programmability and CRISPR\/Cas13a trans-cleavage activity","volume":"91","author":"Shan","year":"2019","journal-title":"Anal. Chem."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib72","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2020.173596","article-title":"Anti-tumor effect of a recombinant Bifidobacterium strain secreting a claudin-targeting molecule in a mouse breast cancer model","volume":"887","author":"Shimizu","year":"2020","journal-title":"Eur. J. Pharmacol."},{"issue":"8","key":"10.1016\/j.jbiotec.2026.04.017_bib73","doi-asserted-by":"crossref","first-page":"876","DOI":"10.3390\/biomedicines9080876","article-title":"TNBC: potential targeting of multiple receptors for a therapeutic breakthrough, nanomedicine, and immunotherapy","volume":"9","author":"Singh","year":"2021","journal-title":"Biomedicines"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib74","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1016\/j.csbj.2021.04.036","article-title":"CRISPR\/Cas9 based genome editing for targeted transcriptional control in triple-negative breast cancer","volume":"19","author":"Singh","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"issue":"4","key":"10.1016\/j.jbiotec.2026.04.017_bib75","doi-asserted-by":"crossref","first-page":"674","DOI":"10.3390\/cells12040674","article-title":"Recent clinical advances on long non-coding RNAs in triple-negative breast cancer","volume":"12","author":"Singh","year":"2023","journal-title":"Cells"},{"issue":"3","key":"10.1016\/j.jbiotec.2026.04.017_bib76","doi-asserted-by":"crossref","DOI":"10.1016\/j.ccell.2019.02.003","article-title":"Logic-gated ROR1 chimeric antigen receptor expression rescues T cell-mediated toxicity to normal tissues and enables selective tumor targeting","volume":"35","author":"Srivastava","year":"2019","journal-title":"Cancer Cell"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib77","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/s42003-024-06555-1","article-title":"CRISPR screens in 3D tumourspheres identified miR-4787-3p as a transcriptional start site miRNA essential for breast tumour-initiating cell growth","volume":"7","author":"Stiff","year":"2024","journal-title":"Commun. Biol."},{"issue":"4","key":"10.1016\/j.jbiotec.2026.04.017_bib78","doi-asserted-by":"crossref","first-page":"4887","DOI":"10.3892\/mmr.2017.7163","article-title":"Long non-coding RNA HOXA11-AS promotes cell proliferation and metastasis in human breast cancer","volume":"16","author":"Su","year":"2017","journal-title":"Mol. Med. Rep."},{"issue":"8","key":"10.1016\/j.jbiotec.2026.04.017_bib79","doi-asserted-by":"crossref","first-page":"830","DOI":"10.3390\/bioengineering11080830","article-title":"Advances in siRNA Drug Delivery Strategies for Targeted TNBC Therapy","volume":"11","author":"Subhan","year":"2024","journal-title":"Bioengineering"},{"issue":"12","key":"10.1016\/j.jbiotec.2026.04.017_bib80","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1158\/2326-6066.CIR-17-0189","article-title":"Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer","volume":"5","author":"Tchou","year":"2017","journal-title":"Cancer Immunol. Res."},{"issue":"2","key":"10.1016\/j.jbiotec.2026.04.017_bib81","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.3390\/ijms24021799","article-title":"An overview of circulating cell-free nucleic acids in diagnosis and prognosis of triple-negative breast cancer","volume":"24","author":"Tierno","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"7","key":"10.1016\/j.jbiotec.2026.04.017_bib82","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1136\/gutjnl-2021-326264","article-title":"Cancer pharmacomicrobiomics: targeting microbiota to optimise cancer therapy outcomes","volume":"71","author":"Ting","year":"2022","journal-title":"Gut"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib83","doi-asserted-by":"crossref","DOI":"10.3389\/fpls.2023.1121209","article-title":"CRISPR\/Cas genome editing in tomato improvement: Advances and applications","volume":"14","author":"Tiwari","year":"2023","journal-title":"Front. Plant Sci."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib84","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2023.1214489","article-title":"CRISPR\/Cas9 as a therapeutic tool for triple negative breast cancer: From bench to clinics","volume":"10","author":"Tiwari","year":"2023","journal-title":"Front. Mol. Biosci."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib85","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.1034707","article-title":"Next generations of CAR-T cells-new therapeutic opportunities in hematology?","volume":"13","author":"Tomasik","year":"2022","journal-title":"Front. Immunol."},{"issue":"12","key":"10.1016\/j.jbiotec.2026.04.017_bib86","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0114900","article-title":"Mesothelin expression in triple negative breast carcinomas correlates significantly with basal-like phenotype, distant metastases and decreased survival","volume":"9","author":"Tozbikian","year":"2014","journal-title":"PloS One"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib87","article-title":"CRISPR\/Cas9: Role of genome editing in cancer immunotherapy","volume":"10","author":"Vimal","year":"2024","journal-title":"Oral. Oncol. Rep."},{"issue":"4","key":"10.1016\/j.jbiotec.2026.04.017_bib88","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3390\/ncrna8040044","article-title":"LncRNA-based classification of triple negative breast cancer revealed inherent tumor heterogeneity and vulnerabilities","volume":"8","author":"Vishnubalaji","year":"2022","journal-title":"Non-coding RNA"},{"issue":"8","key":"10.1016\/j.jbiotec.2026.04.017_bib89","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1016\/j.molonc.2014.07.006","article-title":"miR-206 inhibits cell migration through direct targeting of the actin-binding protein Coronin 1C in triple-negative breast cancer","volume":"8","author":"Wang","year":"2014","journal-title":"Mol. Oncol."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib90","doi-asserted-by":"crossref","DOI":"10.21037\/sci.2018.11.05","article-title":"Current development of chimeric antigen receptor T-cell therapy","volume":"5","author":"Wang","year":"2018","journal-title":"Stem Cell Investig."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib91","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-025-01766-3","article-title":"Engineering bacteria for enhanced tumor therapy: from surface modification to synthetic genetic circuits","author":"Wang","year":"2025","journal-title":"J. Hematol. & Oncol."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib92","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.cell.2014.02.039","article-title":"Integrating biological redesign: where synthetic biology came from and where it needs to go","volume":"157","author":"Way","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib93","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cellimm.2018.05.004","article-title":"A novel AXL chimeric antigen receptor endows T cells with anti-tumor effects against triple negative breast cancers","volume":"331","author":"Wei","year":"2018","journal-title":"Cell. Immunol."},{"issue":"12","key":"10.1016\/j.jbiotec.2026.04.017_bib94","doi-asserted-by":"crossref","first-page":"6745","DOI":"10.3390\/ijms25126745","article-title":"Bcl-2 Up-Regulation Mediates Taxane Resistance Downstream of APC Loss","volume":"25","author":"Wise","year":"2024","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib95","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41392-023-01703-1","article-title":"Camouflaging attenuated Salmonella by cryo-shocked macrophages for tumor-targeted therapy","volume":"9","author":"Wu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"issue":"5","key":"10.1016\/j.jbiotec.2026.04.017_bib96","doi-asserted-by":"crossref","DOI":"10.1002\/cti2.1135","article-title":"EGFR-targeted CAR-T cells are potent and specific in suppressing triple-negative breast cancer both in vitro and in vivo","volume":"9","author":"Xia","year":"2020","journal-title":"Clin. & Transl. Immunol."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib97","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41389-023-00497-9","article-title":"Combined in vitro\/in vivo genome-wide CRISPR screens in triple negative breast cancer identify cancer stemness regulators in paclitaxel resistance","volume":"12","author":"Yan","year":"2023","journal-title":"Oncogenesis"},{"issue":"8","key":"10.1016\/j.jbiotec.2026.04.017_bib98","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/CJI.0000000000000483","article-title":"Mesothelin-targeted CAR-NK cells derived from induced pluripotent stem cells have a high efficacy in killing triple-negative breast cancer cells as shown in several preclinical models","volume":"46","author":"Yang","year":"2023","journal-title":"J. Immunother."},{"issue":"2","key":"10.1016\/j.jbiotec.2026.04.017_bib99","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41388-021-02089-6","article-title":"CRISPR interference and activation of the microRNA-3662-HBP1 axis control progression of triple-negative breast cancer","volume":"41","author":"Yi","year":"2022","journal-title":"Oncogene"},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib100","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13058-020-01296-5","article-title":"Triple-negative breast cancer molecular subtyping and treatment progress","volume":"22","author":"Yin","year":"2020","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-019-1057-4","article-title":"Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity","volume":"18","author":"Yu","year":"2019","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.jbiotec.2026.04.017_bib102","article-title":"T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities","author":"Yu","year":"2026","journal-title":"Adv. Sci."},{"issue":"12","key":"10.1016\/j.jbiotec.2026.04.017_bib103","doi-asserted-by":"crossref","DOI":"10.1002\/biot.202400428","article-title":"Lactobacillus reuteri Assists Engineered Bacteria That Target Tumors to Release PD-L1nb to Mitigate the Adverse Effects of Breast Cancer Immunotherapy","volume":"19","author":"Yue","year":"2024","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib104","doi-asserted-by":"crossref","DOI":"10.1016\/j.copbio.2023.103061","article-title":"Engineering bacteria for cancer immunotherapy","volume":"85","author":"Zalatan","year":"2024","journal-title":"Curr. Opin. Biotechnol."},{"issue":"4","key":"10.1016\/j.jbiotec.2026.04.017_bib105","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.21037\/tcr-24-1087","article-title":"From induced pluripotent stem cell (iPSC) to universal immune cells: literature review of advances in a new generation of tumor therapies","volume":"14","author":"Zhang","year":"2025","journal-title":"Transl. Cancer Res."},{"issue":"3","key":"10.1016\/j.jbiotec.2026.04.017_bib106","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.fmre.2024.11.001","article-title":"Engineered bacteria: Strategies and applications in cancer immunotherapy","volume":"5","author":"Zhang","year":"2025","journal-title":"Fundam. Res."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib107","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s13402-020-00537-1","article-title":"BRD4 modulates vulnerability of triple-negative breast cancer to targeting of integrin-dependent signaling pathways","volume":"43","author":"Zhang","year":"2020","journal-title":"Cell. Oncol."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib108","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41392-023-01375-x","article-title":"Synthetic biology-inspired cell engineering in diagnosis, treatment and drug development","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib109","doi-asserted-by":"crossref","DOI":"10.1016\/j.nano.2019.102146","article-title":"Biomimetic nanovesicles made from iPS cell-derived mesenchymal stem cells for targeted therapy of triple-negative breast cancer","volume":"24","author":"Zhao","year":"2020","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"issue":"7","key":"10.1016\/j.jbiotec.2026.04.017_bib110","doi-asserted-by":"crossref","DOI":"10.21037\/atm.2020.03.194","article-title":"Molecular subtypes and precision treatment of triple-negative breast cancer","volume":"8","author":"Zhao","year":"2020","journal-title":"Ann. Transl. Med."},{"issue":"2","key":"10.1016\/j.jbiotec.2026.04.017_bib111","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41419-022-04537-x","article-title":"DGKZ promotes TGF\u03b2 signaling pathway and metastasis in triple-negative breast cancer by suppressing lipid raft-dependent endocytosis of TGF\u03b2R2","volume":"13","author":"Zhao","year":"2022","journal-title":"Cell Death Dis."},{"issue":"1","key":"10.1016\/j.jbiotec.2026.04.017_bib112","article-title":"Engineered IL-7 receptor enhances the therapeutic effect of AXL-CAR-T cells on triple-negative breast cancer","volume":"2020","author":"Zhao","year":"2020","journal-title":"BioMed. Res. Int."},{"key":"10.1016\/j.jbiotec.2026.04.017_bib113","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3389\/fimmu.2019.01149","article-title":"CAR T cells targeting the tumor MUC1 glycoprotein reduce triple-negative breast cancer growth","volume":"10","author":"Zhou","year":"2019","journal-title":"Front. Immunol."},{"issue":"6","key":"10.1016\/j.jbiotec.2026.04.017_bib114","article-title":"Targeted deprivation of methionine with engineered Salmonella leads to oncolysis and suppression of metastasis in broad types of animal tumor models","volume":"4","author":"Zhou","year":"2023","journal-title":"Cell Rep. Med."}],"container-title":["Journal of Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S016816562600146X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S016816562600146X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T07:06:28Z","timestamp":1783148788000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S016816562600146X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":114,"alternative-id":["S016816562600146X"],"URL":"https:\/\/doi.org\/10.1016\/j.jbiotec.2026.04.017","relation":{},"ISSN":["0168-1656"],"issn-type":[{"value":"0168-1656","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthetic biology-driven innovations in triple-negative breast cancer: Integrating engineering design with targeted therapeutics","name":"articletitle","label":"Article Title"},{"value":"Journal of Biotechnology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbiotec.2026.04.017","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}