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The functional alterations of the E6 and E7 proteins are essential to the oncogenic process of high\u2010risk HPVs and cervical cancer development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The objective of this research is to design highly targeted and efficient small interfering RNAs (siRNAs) that target both HPV16 and HPV18, employing cutting\u2010edge computational approaches to enhance therapeutic potential through a systematic bioinformatics\u2010driven approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>This study utilized the i\u2010Score Designer to identify and evaluate four potential small interfering RNAs (siRNAs) (E6_69, E6_451, E7_66, and E7_193) based on various algorithm criteria, including Ui\u2010Tei, Amarzguioui, i\u2010Score, and Reynolds scores. Consequently, a docking analysis was conducted to elucidate the intermolecular interactions between the RNA\u2010induced silencing complex (RISC) proteins and the designed siRNAs. All siRNAs passed the recommended cutoff values, indicating a strong potential for gene silencing. Thermodynamic and structural analyses revealed that the designed siRNAs had favrable melting temperatures and free energies, suggesting adequate stability for effective gene silencing. Further, docking analysis demonstrated significant binding affinities and interaction profiles with the major RISC proteins (Dicer, Ago2, TRBP). The E6_69 and E7_193 significantly showed strong binding and intermolecular interactions, especially with Ago2, highlighting the potential for HPV gene silencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study revealed the potential of the designed siRNAs in silencing the E6 and E7 genes and their therapeutic applications against HPV. Future research should focus on validating these findings across various experiments, both in\u00a0vivo and in\u00a0vitro, and exploring alternative delivery approaches to enhance therapeutic efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70434","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T05:29:12Z","timestamp":1765776552000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploitation of Biocomputational Approaches for\n                    <scp>siRNA<\/scp>\n                    \u2010Mediated Gene Silencing of\n                    <scp>HPV<\/scp>\n                    : A Novel Therapeutic Strategy for Cervical Cancer"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0055-1895","authenticated-orcid":false,"given":"Md. 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