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

TL;DR

This paper presents a new method for designing siRNAs to target genes involved in liver cancer, achieving strong gene suppression in lab tests.

Contribution

A novel software algorithm and experimental validation for designing effective siRNAs against HCC-related genes.

Findings

A software algorithm was developed for designing both unmodified and modified siRNAs.

Synthesized siRNAs achieved over 50-fold suppression of ITGB1 and CD47 gene expression in vitro.

The method shows potential for creating potent RNA interference-based therapies for hepatocellular carcinoma.

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.

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