A Comprehensive Review of Small Interfering RNAs (siRNAs): Mechanism, Therapeutic Targets, and Delivery Strategies for Cancer Therapy

Int J Nanomedicine. 2023 Dec 13:18:7605-7635. doi: 10.2147/IJN.S436038. eCollection 2023.

Abstract

Small interfering RNA (siRNA) delivery by nanocarriers has been identified as a promising strategy in the study and treatment of cancer. Short nucleotide sequences are synthesized exogenously to create siRNA, which triggers RNA interference (RNAi) in cells and silences target gene expression in a sequence-specific way. As a nucleic acid-based medicine that has gained popularity recently, siRNA exhibits novel potential for the treatment of cancer. However, there are still many obstacles to overcome before clinical siRNA delivery devices can be developed. In this review, we discuss prospective targets for siRNA drug design, explain siRNA drug properties and benefits, and give an overview of the current clinical siRNA therapeutics for the treatment of cancer. Additionally, we introduce the siRNA chemical modifications and delivery systems that are clinically sophisticated and classify bioresponsive materials for siRNA release in a methodical manner. This review will serve as a reference for researchers in developing more precise and efficient targeted delivery systems, promoting ongoing advances in clinical applications.

Keywords: bioresponsive materials; cancer; chemical modifications; delivery systems; small interfering RNA.

Publication types

  • Review

MeSH terms

  • Drug Design
  • Genetic Therapy
  • Humans
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • RNA Interference
  • RNA, Small Interfering / genetics

Substances

  • RNA, Small Interfering

Grants and funding

This work was supported by the Beijing Municipal Fund for Distinguished Young Scholars (Grand No. JQ22022), and National Key R&D Program of China (Grant No. 2022YFF1502000). We appreciate the contribution of the online tool BioRender (https://biorender.com/) to help us create excellent drawings.