{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T21:34:39Z","timestamp":1769636079002,"version":"3.49.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: There is an urgent need for new medications to combat influenza pandemics.<\/jats:p>\n               <jats:p>Methods: Using the genome analysis of the influenza A virus performed previously, we designed and performed a combinatorial exhaustive systematic methodology for optimal design of universal therapeutic small interfering RNA molecules (siRNAs) targeting all diverse influenza A viral strains. The rationale was to integrate the factors for highly efficient design in a pipeline of analysis performed on possible influenza-targeting siRNAs. This analysis selects specific siRNAs that has the ability to target highly conserved, accessible and biologically significant regions. This would require minimal dosage and side effects.<\/jats:p>\n               <jats:p>Results and Discussion: First, &amp;gt;6000 possible siRNAs were designed. Successive filtration followed where a novel method for siRNA scoring filtration layers was implemented. This method excluded siRNAs below the 90% experimental inhibition mapped scores using the intersection of 12 different scoring algorithms. Further filtration of siRNAs is done by eliminating those with off-targets in the human genome and those with undesirable properties and selecting siRNA targeting highly probable single-stranded regions. Finally, the optimal properties of the siRNA were ensured through selection of those targeting 100% conserved, biologically functional short motifs. Validation of a predicted active (sh114) and a predicted inactive (sh113) (that was filtered out in Stage 8) silencer of the NS1 gene showed significant inhibition of the NS1 gene for sh114, with negligible decrease for sh113 which failed target accessibility. This demonstrated the fertility of this methodology.<\/jats:p>\n               <jats:p>Contact: \u00a0mahef@aucegypt.edu<\/jats:p>\n               <jats:p>Supplementary Information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr555","type":"journal-article","created":{"date-parts":[[2011,10,13]],"date-time":"2011-10-13T00:14:29Z","timestamp":1318464869000},"page":"3364-3370","source":"Crossref","is-referenced-by-count":15,"title":["The design of optimal therapeutic small interfering RNA molecules targeting diverse strains of influenza A virus"],"prefix":"10.1093","volume":"27","author":[{"given":"Mahmoud","family":"ElHefnawi","sequence":"first","affiliation":[{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"},{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"},{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"}]},{"given":"Nafisa","family":"Hassan","sequence":"additional","affiliation":[{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"}]},{"given":"Mona","family":"Kamar","sequence":"additional","affiliation":[{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"}]},{"given":"Rania","family":"Siam","sequence":"additional","affiliation":[{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"}]},{"given":"Anna Lisa","family":"Remoli","sequence":"additional","affiliation":[{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"}]},{"given":"Iman","family":"El-Azab","sequence":"additional","affiliation":[{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"}]},{"given":"Osama","family":"AlAidy","sequence":"additional","affiliation":[{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"}]},{"given":"Giulia","family":"Marsili","sequence":"additional","affiliation":[{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"}]},{"given":"Marco","family":"Sgarbanti","sequence":"additional","affiliation":[{"name":"1 Informatics and Systems Department, Division of Engineering Research, National Research Centre, 2Yousef Jameel Science and Technology Research Center, 3Department of Computer Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 4Department of Biology, American University in Cairo, Cairo, Egypt, 5Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanit\u00e0, Viale Regina Elena, 299, 00161 Rome, Italy, 6Department of Information Technology, Faculty of Computers and Information, Cairo University, Cairo, Egypt and 7Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada"}]}],"member":"286","published-online":{"date-parts":[[2011,10,11]]},"reference":[{"key":"2023012511310111700_B1","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.bbrc.2004.02.157","article-title":"An algorithm for selection of functional siRNA sequences","volume":"316","author":"Amarzguioui","year":"2004","journal-title":"Biochem. 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J."},{"key":"2023012511310111700_B10","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1073\/pnas.0437841100","article-title":"RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription","volume":"100","author":"Ge","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012511310111700_B11","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/bit.21798","article-title":"Impact of target mRNA structure on siRNA silencing efficiency: a large-scale study","volume":"100","author":"Gredell","year":"2008","journal-title":"Biotechnol. Bioeng."},{"key":"2023012511310111700_B12","doi-asserted-by":"crossref","first-page":"6909","DOI":"10.1128\/JVI.00081-10","article-title":"Inefficient control of host gene expression by the 2009 pandemic H1N1 influenza A virus NS1 protein","volume":"84","author":"Hale","year":"2010","journal-title":"J. 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Biol."},{"key":"2023012511310111700_B14","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1093\/nar\/gkh238","article-title":"A library of siRNA duplexes targeting the phosphoinositide 3-kinase pathway: determinants of gene silencing for use in cell-based screens","volume":"32","author":"Hsieh","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2023012511310111700_B15","doi-asserted-by":"crossref","first-page":"D690","DOI":"10.1093\/nar\/gkn828","article-title":"Ensembl 2009","volume":"37","author":"Hubbard","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012511310111700_B16","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/nbt1118","article-title":"Design of a genome-wide siRNA library using an artificial neural network","volume":"23","author":"Huesken","year":"2005","journal-title":"Nat. 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Transplant."},{"key":"2023012511310111700_B19","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1261\/rna.30706","article-title":"Position-specific chemical modification of siRNAs reduces \u201coff-target\u201d transcript silencing","volume":"12","author":"Jackson","year":"2006","journal-title":"RNA"},{"key":"2023012511310111700_B20","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1261\/rna.25706","article-title":"Widespread siRNA \u201coff-target\u201d transcript silencing mediated by seed region sequence complementarity","volume":"12","author":"Jackson","year":"2006","journal-title":"RNA"},{"key":"2023012511310111700_B21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrd3010","article-title":"Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application","volume":"9","author":"Jackson","year":"2010","journal-title":"Nat. Rev. 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