Approach to Design of Potent RNA Interference-Based Preparations Against Hepatocellular Carcinoma-Related Genes

Sep 22, 2026

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Every year, advances in healthcare continue to grow, yet oncological pathologies keep expanding in their overall burden, despite improvements in quality of life and longevity. For hepatocellular carcinoma (HCC), conventional therapies such as surgery or chemotherapy often show unstable performance because of the cancer’s highly heterogeneous nature. The study proposes a design framework for potent siRNAs using RNA interference against ITGB1 and CD47 mRNAs, including software-guided siRNA design, solid-phase synthesis, and in vitro validation showing over 50-fold gene expression suppression.

LanguageEnglish

CategoryResearch & Report

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Pages14

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Article Approach to Design of Potent RNA Interference-Based Preparations Against Hepatocellular Carcinoma-Related Genes Petr V. Chernov 1, Vladimir N. Ivanov 1, Nikolai A. Dmitriev 1, Artem E. Gusev 1, Valeriia I. Kovchina 1, Ivan S. Gongadze 1, Alexander V. Kholstov 1, Maiia V. Popova 1, Dmitry A. Kudlay 1,2,3, Daria S. Kryuchko 4,5,6, Ilya A. Kofiadi 1,7, * and Musa R. Khaitov 1,7 Academic Editor: Mohamed Raafat El-Gewely Received: 25 November 2025 Revised: 31 December 2025 Accepted: 5 January 2026 Published: 7 January 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 NRC Institute of Immunology FMBA of Russia, 115522 Moscow, Russia; [496ram496@gmail.com](496ram496@gmail.com) (P.V.C.); [kvi-91@mail.ru](kvi-91@mail.ru) (V.I.K.); [ivan.gongadze@gmail.com](ivan.gongadze@gmail.com) (I.S.G.) 2 A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov 1st Moscow State Medical University of the MOH of Russia (Sechenov University), 119992 Moscow, Russia 3 Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, 119991 Moscow, Russia 4 Federal Medical-Biological Agency, 123182 Moscow, Russia 5 The Institute of Neonatology and Pediatrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 117198 Moscow, Russia 6 Neonatology Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia 7 Medical Biological Faculty, Pirogov Russian National Research Medical University, 117513 Moscow, Russia * [Correspondence: kofiadi@gmail.com](Correspondence: kofiadi@gmail.com) Abstract Every year, the scientific community continues to drive advances in healthcare, opening up new perspectives in the treatment and management of various diseases. Despite vast strides being made in the quality of life and longevity, we still face an equally significant growth in the burden of oncological pathologies. Although current trends lean towards preventive and personalized medicine, numerous hurdles remain to be cleared to develop robust strategies in the field of oncology. Among all types of tumors, one of the prominent positions is occupied by hepatocellular carcinoma (HCC), which is one of the most widespread primary cancers with a high mortality rate. Conventional approaches to HCC therapy, such as surgery or chemotherapy, rarely provide steady performance due to the highly polymorphous nature of the cancerous process. In this study, we suggest an alternative methodological framework for designing potent siRNAs targeting genes implicated in hepatocellular carcinoma, implementing RNA interference mediated by synthetic small interfering RNAs (siRNAs) against mRNAs of ITGB1 and CD47 genes. Products of these genes are renowned drivers of tumor progression. We have developed a software algorithm for the design of unmodified and modified siRNAs, carried out solid-phase synthesis of the most promising molecules, and proved their capability to perform a more than 50-fold suppression of expression of the target genes in vitro. Keywords: siRNA; RNAi; hepatocellular carcinoma; HCC; ITGB1; CD47; in silico drug design 1. Introduction Hepatocellular carcinoma (HCC) is an oncological pathology characterized by themalignization of hepatocytes, the formation of tumors, and metastases. HCC is one of the most prevalent primary hepatic cancers, ranking fourth in cancer-related mortality causes worldwide [1] . Akin to the majority of oncological processes, HCC may be characterized according to the Hallmarks of cancer [2] . The pathogenesis is tightly linked to the dysregulation of cellular metabolism and gen

FAQs

Why is hepatocellular carcinoma (HCC) challenging to treat with conventional methods?

HCC therapies such as surgery or chemotherapy often provide unstable results because the cancer process is highly heterogeneous and adapts to treatment.

What RNA interference targets were proposed in this study?

The study designs siRNAs targeting the ITGB1 and CD47 genes implicated in hepatocellular carcinoma progression.

How was siRNA performance evaluated?

A software algorithm supported the design of unmodified and modified siRNAs, followed by solid-phase synthesis of promising molecules and in vitro testing showing more than 50-fold suppression of target gene expression.

Sep 22, 2026

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