title: The design of optimal therapeutic small interfering RNA molecules targeting diverse strains of influenza A virus.
abstract: BACKGROUND
  There is an urgent need for new medications to combat influenza pandemics.
  
  
  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.
  
  
  CONCLUSIONS
  First, >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.
  
  
  BACKGROUND
  mahef@aucegypt.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors: Informatics and Systems Department, Division of Engineering Research, National Research Centre, Egypt. mahef@aucegypt.edu
authors: Mahmoud
authors: M
authors: ElHefnawi
authors: Nafisa
authors: N
authors: Hassan
authors: Mona
authors: M
authors: Kamar
authors: Rania
authors: R
authors: Siam
authors: Anna Lisa
authors: AL
authors: Remoli
authors: Iman
authors: I
authors: El-Azab
authors: Osama
authors: O
authors: AlAidy
authors: Giulia
authors: G
authors: Marsili
authors: Marco
authors: M
authors: Sgarbanti
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000502:physiology; D009980:Influenza A virus / Q000145:classification* / Q000235:genetics*; D007251:Influenza, Human / Q000235:genetics / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics*; D012984:Software
chemical_list: D034741:RNA, Small Interfering