Fungal ribotoxins are a family of proteins with the ability to induce cell death, whereby considered as effective candidate for anti-cancer drugs. However, the success of this strategy is dependent to cancer cells selection without toxicity effects to normal tissues. Bearing in mind, designing a new generation of genetics construct for targeting colon cancer were performed in this study based on application of the Hirsutellin A as smaller ribotoxin. In this regard, NCBI, Uniprot and ExPASy databanks were used for accessing to Protein and nucleotide sequences of the selected genes. Moreover, CD search program were used for detection active domins. On the other hand, cell surface specific antigens of the colon cancer were gathered based on literature and evaluated by Proteinatlas database. Meanwhlie, corresponding ligands of the selected antigens were investigated through string program. Besides, Cluspro, Pymol, Rampage as well as IEDB, ProPred-I and Propred databases and programs were used for calculating binding energy, quality of the structure and immunogenicity character of the constructs. Taken together, the results of this study led to the introduction a cell death domain in the Hirsutellin A, as well as GPA33 as a cell surface specific antigens of the colon cancer with seven coreesponding ligands. More analysis led to ligands miniaturization based on amino acids charactrization. Moreover, seven novel genetic constructs were designed based on the assembly of the selected domains. Finally, HTA-(GGGGS)3-HSF showed the highest quality in the structure and immunogenicity among designed constructs that ought to investigated under experimental condition.

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