Chemical and structural modifications of RNAi therapeutics

Sook Hee Ku, Sung Duk Jo, Yeon Kyung Lee, Kwangmeyung Kim, Sun Hwa Kim

Research output: Contribution to journalReview articlepeer-review

123 Scopus citations

Abstract

Small interfering RNA (siRNA), a 21–23 nt double-stranded RNA responsible for post-transcriptional gene silencing, has attracted great interests as promising genomic drugs, due to its strong ability to silence target genes in a sequence-specific manner. Despite high silencing efficiency and on-target specificity, the clinical translation of siRNA has been hindered by its inherent features: poor intracellular delivery, limited blood stability, unpredictable immune responses and unwanted off-targeting effects. To overcome these hindrances, researchers have made various advances to modify siRNA itself and to improve its delivery. In this review paper, first we briefly discuss the innate properties and delivery barriers of siRNA. Then, we describe recent progress in (1) chemically and structurally modified siRNAs to solve their intrinsic problems and (2) siRNA delivery formulations including siRNA conjugates, polymerized siRNA, and nucleic acid-based nanoparticles to improve in vivo delivery.

Original languageEnglish
Pages (from-to)16-28
Number of pages13
JournalAdvanced Drug Delivery Reviews
Volume104
DOIs
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2015 Elsevier B.V.

Keywords

  • Chemical modification
  • RNA interference
  • Structural modification
  • siRNA
  • siRNA delivery

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