Molecularly engineered siRNA conjugates for tumor-targeted RNAi therapy

Jong Won Lee, Jiwon Choi, Yeonho Choi, Kwangmeyung Kim, Yoosoo Yang, Sun Hwa Kim, Hong Yeol Yoon, Ick Chan Kwon

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy.

Original languageEnglish
Pages (from-to)713-726
Number of pages14
JournalJournal of Controlled Release
Publication statusPublished - 2022 Nov

Bibliographical note

Publisher Copyright:
© 2022


  • Gene delivery
  • RNA interference
  • Small interfering RNA
  • cancer therapy
  • siRNA conjugates

ASJC Scopus subject areas

  • Pharmaceutical Science


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