{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:04:05Z","timestamp":1789707845380,"version":"4.0.1"},"reference-count":102,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wenzhou-Kean University","award":["5000105"],"award-info":[{"award-number":["5000105"]}],"id":[{"id":"https:\/\/ror.org\/05609xa16","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wenzhou-Kean University","award":["WB20240221000037"],"award-info":[{"award-number":["WB20240221000037"]}],"id":[{"id":"https:\/\/ror.org\/05609xa16","id-type":"ROR","asserted-by":"crossref"}]},{"award":["5000105"],"award-info":[{"award-number":["5000105"]}],"id":[{"id":"https:\/\/ror.org\/05609xa16","id-type":"ROR","asserted-by":"publisher"}]},{"award":["WB20240221000037"],"award-info":[{"award-number":["WB20240221000037"]}],"id":[{"id":"https:\/\/ror.org\/05609xa16","id-type":"ROR","asserted-by":"publisher"}]},{"name":"IFIRI Talents Program","award":["KY20250604000448"],"award-info":[{"award-number":["KY20250604000448"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Antimicrobial resistance has renewed interest in live therapeutic phages, including engineered candidates and defined phage cocktails, as antibacterial strategies. However, clinical translation requires evidence extending beyond phage isolation and computational prediction. This review examines how phage genomics and bioinformatics can support phage-based antibacterial development while remaining aligned with pharmaceutical requirements for safety, quality, pharmacology, and clinical validation. Methods: This narrative review synthesizes the literature on the generation, interpretation, and experimental validation of genomic and bioinformatic evidence for live therapeutic phages. Representative approaches for viral identification, genome-quality assessment, annotation, comparative genomics, lytic\u2013temperate lifestyle classification, host prediction, receptor analysis, antiphage-defence profiling, and artificial-intelligence-assisted prioritization were evaluated according to their outputs, principal failure modes, validation requirements, and supported development decisions. Results: Current tools address distinct analytical tasks. Examples include VIBRANT and geNomad for viral identification, CheckV and PhageTerm for genome-quality and termini assessment, Pharokka, PHANOTATE, and PHROGs for gene prediction and annotation, PhageAI, BACPHLIP, and PhaTYP for lytic\u2013temperate lifestyle prediction, iPHoP and CRISPR spacer matching for host prioritization, and PADLOC and DefenseFinder for bacterial defence profiling. Their outputs differ in taxonomic resolution, reference coverage, training-data dependence, and biological interpretation. The review maps these outputs to proportionate validation requirements while integrating formulation and PK\/PD context, sequence-to-product traceability, intellectual-property documentation, minimum-information reporting, and resistance-responsive redesign. Conclusions: This review presents a practical sequence-to-product framework for interpreting contemporary phage-bioinformatics methods. By separating computational discovery from isolate-level activity, product quality, pharmacological evidence, and clinical monitoring, it clarifies the decisions supported at each stage and the additional evidence required before candidate progression, product use, or redesign.<\/jats:p>","DOI":"10.3390\/ph19091465","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:58:59Z","timestamp":1789545539000},"page":"1465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phage Genomics and Bioinformatics in Therapeutic Development: Evidence Limits, Validation Gates, and Translational Decision-Making"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2709-6754","authenticated-orcid":false,"given":"Mia Yang","family":"Ang","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Jeffrey Cheah Sunway Medical School, Faculty of Medical and Life Sciences, Sunway University, Sunway City, Petaling Jaya 47500, Selangor, Malaysia"},{"name":"Sunway Microbiome Centre, Faculty of Medical and Life Sciences, Sunway University, Sunway City, Petaling Jaya 47500, Selangor, Malaysia"},{"name":"Zhejiang-Malaysia Joint Laboratory for Rare Medicinal Resources, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang-Malaysia Joint Laboratory for Rare Medicinal Resources, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"},{"name":"College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanni","family":"Song","sequence":"additional","affiliation":[{"name":"Zhejiang-Malaysia Joint Laboratory for Rare Medicinal Resources, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"},{"name":"College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Lipovich","sequence":"additional","affiliation":[{"name":"Zhejiang-Malaysia Joint Laboratory for Rare Medicinal Resources, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"},{"name":"College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew Woh","family":"Choo","sequence":"additional","affiliation":[{"name":"Zhejiang-Malaysia Joint Laboratory for Rare Medicinal Resources, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"},{"name":"College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"},{"name":"Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA"},{"name":"International Frontier Interdisciplinary Research Institute (IFIRI), Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","unstructured":"Antimicrobial Resistance Collaborators (2022). Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet, 399, 629\u2013655."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.4292\/wjgpt.v8.i3.162","article-title":"Phage therapy: An alternative to antibiotics in the age of multi-drug resistance","volume":"8","author":"Lin","year":"2017","journal-title":"World J. Gastrointest. Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1093\/femsre\/fuaa017","article-title":"Current challenges and future opportunities of phage therapy","volume":"44","author":"Pires","year":"2020","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fuerst-Wilmes, M., Respondek, V., Schramm, M., Lilienthal, N., Buss, K., and Duechting, A. (2025). Regulation of phage therapy medicinal products: Developments, challenges, and opportunities. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1631359"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e187996","DOI":"10.1172\/JCI187996","article-title":"Bacteriophage therapy for multidrug-resistant infections: Current technologies and therapeutic approaches","volume":"135","author":"Kim","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nikolich, M.P., and Filippov, A.A. (2020). Bacteriophage Therapy: Developments and Directions. Antibiotics, 9.","DOI":"10.3390\/antibiotics9030135"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"elaf011","DOI":"10.1093\/bfgp\/elaf011","article-title":"Genomic insights into bacteriophages: A new frontier in AMR detection and phage therapy","volume":"24","author":"Banerjee","year":"2025","journal-title":"Brief. Funct. Genom."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s40168-020-00867-0","article-title":"VIBRANT: Automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences","volume":"8","author":"Kieft","year":"2020","journal-title":"Microbiome"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41587-020-00774-7","article-title":"CheckV assesses the quality and completeness of metagenome-assembled viral genomes","volume":"39","author":"Nayfach","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S352","DOI":"10.1093\/cid\/ciad539","article-title":"Knowing and Naming: Phage Annotation and Nomenclature for Phage Therapy","volume":"77","author":"Grigson","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","unstructured":"U.S. Food and Drug Administration (2026, July 31). Investigational New Drug Applications (INDs) for CBER-Regulated Products, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/development-approval-process-cber\/investigational-new-drug-applications-inds-cber-regulated-products."},{"key":"ref_12","unstructured":"European Medicines Agency (2025). Draft Guideline on Quality Aspects of Phage Therapy Medicinal Products, EMA\/CHMP\/BWP\/1\/2024."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/femsre\/fuv048","article-title":"Computational approaches to predict bacteriophage-host relationships","volume":"40","author":"Edwards","year":"2016","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nami, Y., Imeni, N., and Panahi, B. (2021). Application of machine learning in bacteriophage research. BMC Microbiol., 21.","DOI":"10.1186\/s12866-021-02256-5"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Abdraimova, N., Shitikov, E., and Kornienko, M. (2026). The Role of Genomics in Advancing and Standardising Bacteriophage Therapy. Antibiotics, 15.","DOI":"10.3390\/antibiotics15010055"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Murray, E., Draper, L.A., Ross, R.P., and Hill, C. (2021). The Advantages and Challenges of Using Endolysins in a Clinical Setting. Viruses, 13.","DOI":"10.3390\/v13040680"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev-med-080219-122208","article-title":"Phage Therapy for Antibiotic-Resistant Bacterial Infections","volume":"73","author":"Hatfull","year":"2022","journal-title":"Annu. Rev. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102426","DOI":"10.1016\/j.mib.2024.102426","article-title":"Biological and bioinformatic tools for the discovery of unknown phage-host combinations","volume":"77","author":"Mahony","year":"2024","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hitchcock, N.M., Devequi Gomes Nunes, D., Shiach, J., Valeria Saraiva Hodel, K., Dantas Viana Barbosa, J., Alencar Pereira Rodrigues, L., Coler, B.S., Botelho Pereira Soares, M., and Badaro, R. (2023). Current Clinical Landscape and Global Potential of Bacteriophage Therapy. Viruses, 15.","DOI":"10.3390\/v15041020"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.2174\/1389201024666221104142457","article-title":"Bacteriophages Concept and Applications: A Review on Phage Therapy","volume":"24","author":"Sahu","year":"2023","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_21","first-page":"4","article-title":"A Forgotten Phage Thinker: Bacteriophage Research in USSR in 1930s and the Contribution by Professor M.I. Lurie","volume":"7","author":"Letarov","year":"2026","journal-title":"Phage"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1146\/annurev-virology-100422-040919","article-title":"The Cold War and Phage Therapy: How Geopolitics Stalled Development of Viruses as Antibacterials","volume":"11","author":"Summers","year":"2024","journal-title":"Annu. Rev. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ribes-Martinez, L., Munoz-Egea, M.C., Yuste, J., Esteban, J., and Garcia-Quintanilla, M. (2024). Bacteriophage Therapy as a Promising Alternative for Antibiotic-Resistant Enterococcus faecium: Advances and Challenges. Antibiotics, 13.","DOI":"10.3390\/antibiotics13121120"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/cid\/ciy947","article-title":"A Systematic and Critical Review of Bacteriophage Therapy Against Multidrug-resistant ESKAPE Organisms in Humans","volume":"69","author":"Harb","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e208","DOI":"10.1016\/S1473-3099(21)00612-5","article-title":"Safety and efficacy of phage therapy in difficult-to-treat infections: A systematic review","volume":"22","author":"Uyttebroek","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e70090","DOI":"10.1002\/jobm.70090","article-title":"Bacteriophage Therapy to Combat Microbial Infections and Antimicrobial Resistance","volume":"65","author":"Sharma","year":"2025","journal-title":"J. Basic Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.3390\/idr16060092","article-title":"Advancing Phage Therapy: A Comprehensive Review of the Safety, Efficacy, and Future Prospects for the Targeted Treatment of Bacterial Infections","volume":"16","author":"Palma","year":"2024","journal-title":"Infect. Dis. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00066-18","DOI":"10.1128\/CMR.00066-18","article-title":"Phage Therapy in the Postantibiotic Era","volume":"32","author":"Barr","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.chom.2019.01.014","article-title":"Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria","volume":"25","author":"Kortright","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8572","DOI":"10.1038\/s41467-024-52595-w","article-title":"Targeting Pseudomonas aeruginosa biofilm with an evolutionary trained bacteriophage cocktail exploiting phage resistance trade-offs","volume":"15","author":"Kunisch","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-1-0716-3523-0_4","article-title":"Guidelines to Compose an Ideal Bacteriophage Cocktail","volume":"2734","author":"Merabishvili","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"McCallin, S., Sacher, J.C., Zheng, J., and Chan, B.K. (2019). Current State of Compassionate Phage Therapy. Viruses, 11.","DOI":"10.3390\/v11040343"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pirnay, J.P., Verbeken, G., Ceyssens, P.J., Huys, I., De Vos, D., Ameloot, C., and Fauconnier, A. (2018). The Magistral Phage. Viruses, 10.","DOI":"10.3390\/v10020064"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1021\/acs.chemrev.4c00681","article-title":"Engineering Phages to Fight Multidrug-Resistant Bacteria","volume":"125","author":"Peng","year":"2025","journal-title":"Chem. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1128\/MMBR.00069-15","article-title":"Genetically Engineered Phages: A Review of Advances over the Last Decade","volume":"80","author":"Pires","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/phar.2358","article-title":"Bacteriophage Therapeutics: A Primer for Clinicians on Phage-Antibiotic Combinations","volume":"40","author":"Morrisette","year":"2020","journal-title":"Pharmacotherapy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e0182225","DOI":"10.1128\/mbio.01822-25","article-title":"Reprogramming resistance: Phage-antibiotic synergy targets efflux systems in ESKAPEE pathogens","volume":"16","author":"Tarasenko","year":"2025","journal-title":"mBio"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"001895","DOI":"10.1099\/jmm.0.001895","article-title":"Current status of clinical trials for phage therapy","volume":"73","author":"Uchechukwu","year":"2024","journal-title":"J. Med. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1038\/s41467-025-60598-4","article-title":"Phage therapy with nebulized cocktail BX004-A for chronic Pseudomonas aeruginosa infections in cystic fibrosis: A randomized first-in-human trial","volume":"16","author":"Weiner","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev-virology-012423-110530","article-title":"Developing Phage Therapy That Overcomes the Evolution of Bacterial Resistance","volume":"10","author":"Antani","year":"2023","journal-title":"Annu. Rev. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.cmi.2023.01.021","article-title":"Pharmacokinetics\/pharmacodynamics of phage therapy: A major hurdle to clinical translation","volume":"29","author":"Nang","year":"2023","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gorski, A., Borysowski, J., and Miedzybrodzki, R. (2020). Phage Therapy: Towards a Successful Clinical Trial. Antibiotics, 9.","DOI":"10.3390\/antibiotics9110827"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Stone, E., Campbell, K., Grant, I., and McAuliffe, O. (2019). Understanding and Exploiting Phage-Host Interactions. Viruses, 11.","DOI":"10.3390\/v11060567"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12941-020-00389-5","article-title":"Bacteriophage therapy against Pseudomonas aeruginosa biofilms: A review","volume":"19","author":"Chegini","year":"2020","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"fnw002","DOI":"10.1093\/femsle\/fnw002","article-title":"Host receptors for bacteriophage adsorption","volume":"363","author":"Storms","year":"2016","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jurado, A., Fernandez, L., Rodriguez, A., and Garcia, P. (2022). Understanding the Mechanisms That Drive Phage Resistance in Staphylococci to Prevent Phage Therapy Failure. Viruses, 14.","DOI":"10.3390\/v14051061"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Abedon, S.T., Danis-Wlodarczyk, K.M., Wozniak, D.J., and Sullivan, M.B. (2021). Improving Phage-Biofilm In Vitro Experimentation. Viruses, 13.","DOI":"10.3390\/v13061175"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.cis.2017.05.014","article-title":"Formulation, stabilisation and encapsulation of bacteriophage for phage therapy","volume":"249","author":"Malik","year":"2017","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cell.2022.11.017","article-title":"Phage therapy: From biological mechanisms to future directions","volume":"186","author":"Strathdee","year":"2023","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1146\/annurev-virology-100114-054915","article-title":"Bacteriophage Therapy: Advances in Formulation Strategies and Human Clinical Trials","volume":"2","author":"Vandenheuvel","year":"2015","journal-title":"Annu. Rev. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.copbio.2021.03.002","article-title":"Preclinical data and safety assessment of phage therapy in humans","volume":"68","author":"Nale","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1080\/03009734.2019.1688433","article-title":"Pharmacological limitations of phage therapy","volume":"124","author":"Nilsson","year":"2019","journal-title":"Ups. J. Med. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7055","DOI":"10.1007\/s11033-023-08557-4","article-title":"Bacteriophage genome engineering for phage therapy to combat bacterial antimicrobial resistance as an alternative to antibiotics","volume":"50","author":"Usman","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1039\/C5IB00267B","article-title":"Genetically modified bacteriophages","volume":"8","author":"Sagona","year":"2016","journal-title":"Integr. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/nbt.3043","article-title":"Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials","volume":"32","author":"Bikard","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/nbt.3011","article-title":"Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases","volume":"32","author":"Citorik","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.copbio.2020.11.003","article-title":"Enhancing phage therapy through synthetic biology and genome engineering","volume":"68","author":"Lenneman","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Torres-Barcelo, C. (2018). Phage Therapy Faces Evolutionary Challenges. Viruses, 10.","DOI":"10.3390\/v10060323"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.copbio.2020.11.011","article-title":"Phage-specific antibodies","volume":"68","author":"Gembara","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/s41587-023-01953-y","article-title":"Identification of mobile genetic elements with geNomad","volume":"42","author":"Camargo","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8292","DOI":"10.1038\/s41598-017-07910-5","article-title":"PhageTerm: A tool for fast and accurate determination of phage termini and packaging mechanism using next-generation sequencing data","volume":"7","author":"Garneau","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"btac776","DOI":"10.1093\/bioinformatics\/btac776","article-title":"Pharokka: A fast scalable bacteriophage annotation tool","volume":"39","author":"Bouras","year":"2023","journal-title":"Bioinformatics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4537","DOI":"10.1093\/bioinformatics\/btz265","article-title":"PHANOTATE: A novel approach to gene identification in phage genomes","volume":"35","author":"McNair","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"lqab067","DOI":"10.1093\/nargab\/lqab067","article-title":"PHROG: Families of prokaryotic virus proteins clustered using remote homology","volume":"3","author":"Terzian","year":"2021","journal-title":"NAR Genom. Bioinform."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Moraru, C., Varsani, A., and Kropinski, A.M. (2020). VIRIDIC-A Novel Tool to Calculate the Intergenomic Similarities of Prokaryote-Infecting Viruses. Viruses, 12.","DOI":"10.1101\/2020.07.05.188268"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/978-1-0716-3838-5_14","article-title":"Comparative Analyses of Bacteriophage Genomes","volume":"2802","author":"Rossi","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e11396","DOI":"10.7717\/peerj.11396","article-title":"BACPHLIP: Predicting bacteriophage lifestyle from conserved protein domains","volume":"9","author":"Hockenberry","year":"2021","journal-title":"PeerJ"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"bbac487","DOI":"10.1093\/bib\/bbac487","article-title":"PhaTYP: Predicting the lifestyle for bacteriophages using BERT","volume":"24","author":"Shang","year":"2023","journal-title":"Brief. Bioinform."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tynecki, P., Guzi\u0144ski, A., Kazimierczak, J., Jadczuk, M., Dastych, J., and Onisko, A. (2020). PhageAI\u2014Bacteriophage Life Cycle Recognition with Machine Learning and Natural Language Processing. bioRxiv.","DOI":"10.1101\/2020.07.11.198606"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Roux, S., Camargo, A.P., Coutinho, F.H., Dabdoub, S.M., Dutilh, B.E., Nayfach, S., and Tritt, A. (2023). iPHoP: An integrated machine learning framework to maximize host prediction for metagenome-derived viruses of archaea and bacteria. PLoS Biol., 21.","DOI":"10.1371\/journal.pbio.3002083"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1093\/nar\/gkab133","article-title":"Streamlining CRISPR spacer-based bacterial host predictions to decipher the viral dark matter","volume":"49","author":"Dion","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"115369","DOI":"10.1016\/j.celrep.2025.115369","article-title":"Characterization and host range prediction of Staphylococcus aureus phages through receptor-binding protein analysis","volume":"44","author":"Krusche","year":"2025","journal-title":"Cell Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10868","DOI":"10.1093\/nar\/gkab883","article-title":"Identification and classification of antiviral defence systems in bacteria and archaea with PADLOC reveals new system types","volume":"49","author":"Payne","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1038\/s41467-022-30269-9","article-title":"Systematic and quantitative view of the antiviral arsenal of prokaryotes","volume":"13","author":"Tesson","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e0320623","DOI":"10.1128\/mbio.03206-23","article-title":"Improving viral annotation with artificial intelligence","volume":"15","author":"Flamholz","year":"2024","journal-title":"mBio"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Niazi, S.K. (2025). Bacteriophage Therapy: Discovery, Development, and FDA Approval Pathways. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081115"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41579-019-0311-5","article-title":"Phage diversity, genomics and phylogeny","volume":"18","author":"Dion","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.coviro.2021.12.004","article-title":"Digital phagograms: Predicting phage infectivity through a multilayer machine learning approach","volume":"52","author":"Lood","year":"2022","journal-title":"Curr. Opin. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"bbag085","DOI":"10.1093\/bib\/bbag085","article-title":"Towards accurate artificial intelligence models for strain-level phage-host prediction","volume":"27","author":"Malajczuk","year":"2026","journal-title":"Brief. Bioinform."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"bbaf626","DOI":"10.1093\/bib\/bbaf626","article-title":"From genomic signals to prediction tools: A critical feature analysis and rigorous benchmark for phage-host prediction","volume":"26","author":"Shang","year":"2025","journal-title":"Brief. Bioinform."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-0716-3523-0_6","article-title":"Bacteriophage Production in Compliance with Regulatory Requirements","volume":"2734","author":"Pirnay","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1016\/j.chom.2024.09.004","article-title":"Rapid design of bacteriophage cocktails to suppress the burden and virulence of gut-resident carbapenem-resistant Klebsiella pneumoniae","volume":"32","author":"Rotman","year":"2024","journal-title":"Cell Host Microbe"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Diallo, K., and Dublanchet, A. (2022). Benefits of Combined Phage-Antibiotic Therapy for the Control of Antibiotic-Resistant Bacteria: A Literature Review. Antibiotics, 11.","DOI":"10.3390\/antibiotics11070839"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"fuab048","DOI":"10.1093\/femsre\/fuab048","article-title":"Mechanisms and clinical importance of bacteriophage resistance","volume":"46","author":"Egido","year":"2022","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"S384","DOI":"10.1093\/cid\/ciad497","article-title":"Therapeutic Phage Monitoring: A Review","volume":"77","author":"Bosco","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5629","DOI":"10.2147\/IDR.S341265","article-title":"Risk of Bacteriophage Therapeutics to Transfer Genetic Material and Contain Contaminants Beyond Endotoxins with Clinically Relevant Mitigation Strategies","volume":"14","author":"Doub","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.tim.2018.10.008","article-title":"Phage Therapy: Going Temperate?","volume":"27","author":"Monteiro","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e0207121","DOI":"10.1128\/aac.02071-21","article-title":"Considerations for the Use of Phage Therapy in Clinical Practice","volume":"66","author":"Suh","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e0029523","DOI":"10.1128\/spectrum.00295-23","article-title":"Biological characterization and genomic analysis of a novel methicillin-resistant Staphylococcus aureus phage, SauPS-28","volume":"12","author":"Zhao","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Liu, D., Van Belleghem, J.D., de Vries, C.R., Burgener, E., Chen, Q., Manasherob, R., Aronson, J.R., Amanatullah, D.F., Tamma, P.D., and Suh, G.A. (2021). The Safety and Toxicity of Phage Therapy: A Review of Animal and Clinical Studies. Viruses, 13.","DOI":"10.20944\/preprints202105.0231.v1"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/j.clinthera.2020.07.014","article-title":"Phage Therapy in the Resistance Era: Where Do We Stand and Where Are We Going?","volume":"42","author":"Luong","year":"2020","journal-title":"Clin. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e0139324","DOI":"10.1128\/mbio.01393-24","article-title":"Phage-antibiotic synergy suppresses resistance emergence of Klebsiella pneumoniae by altering the evolutionary fitness","volume":"15","author":"Qin","year":"2024","journal-title":"mBio"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e0004424","DOI":"10.1128\/cmr.00044-24","article-title":"Pharmacokinetics and pharmacodynamics of bacteriophage therapy: A review with a focus on multidrug-resistant Gram-negative bacterial infections","volume":"37","author":"Siopi","year":"2024","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1093\/jac\/dkw083","article-title":"Bacteriophage therapy: A regulatory perspective","volume":"71","author":"Pelfrene","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Yang, Q., Le, S., Zhu, T., and Wu, N. (2023). Regulations of phage therapy across the world. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1250848"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1093\/cid\/ciad335","article-title":"A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes","volume":"77","author":"Green","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_97","unstructured":"European Patent Office (2026, July 31). Patentable Biotechnological Inventions. Available online: https:\/\/www.epo.org\/en\/legal\/guidelines-epc\/2026\/g_ii_5_2.html."},{"key":"ref_98","unstructured":"World Intellectual Property Organization (2024). WIPO Standard ST.26: Presentation of Nucleotide and Amino Acid Sequence Listings Using XML, World Intellectual Property Organization."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.chom.2022.09.017","article-title":"An expanded arsenal of immune systems that protect bacteria from phages","volume":"30","author":"Millman","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"128231","DOI":"10.1016\/j.micres.2025.128231","article-title":"Bacteriophage therapy for critical antibiotic-resistant Gram-positive bacteria: A systematic review of clinical researches","volume":"298","author":"Nie","year":"2025","journal-title":"Microbiol. Res."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Willy, C., Bugert, J.J., Classen, A.Y., Deng, L., Duchting, A., Gross, J., Hammerl, J.A., Korf, I.H.E., Kuhn, C., and Lieberknecht-Jouy, S. (2023). Phage Therapy in Germany-Update 2023. Viruses, 15.","DOI":"10.3390\/v15020588"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nbt.4306","article-title":"Minimum Information about an Uncultivated Virus Genome (MIUViG)","volume":"37","author":"Roux","year":"2019","journal-title":"Nat. Biotechnol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1465\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:17:34Z","timestamp":1789705054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":102,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ph19091465"],"URL":"https:\/\/doi.org\/10.3390\/ph19091465","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}