Hydrophobization and bioconjugation for enhanced siRNA delivery and targeting

Daniel De Paula, M. Vitória L.B. Bentley, Ram I. Mahato

Research output: Contribution to journalReview articlepeer-review

196 Scopus citations


RNA interference (RNAi) is an evolutionarily conserved process by which double-stranded small interfering RNA (siRNA) induces sequence-specific, post-transcriptional gene silencing. Unlike other mRNA targeting strategies, RNAi takes advantage of the physiological gene silencing machinery. The potential use of siRNA as therapeutic agents has attracted great attention as a novel approach for treating severe and chronic diseases. RNAi can be achieved by either delivery of chemically synthesized siRNAs or endogenous expression of small hairpin RNA, siRNA, and microRNA (miRNA). However, the relatively high dose of siRNA required for gene silencing limits its therapeutic applications. This review discusses several strategies to improve therapeutic efficacy as well as to abrogate off-target effects and immunostimulation caused by siRNAs. There is an in-depth discussion on various issues related to the (1) mechanisms of RNAi, (2) methods of siRNA production, (3) barriers to RNAi-based therapies, (4) biodistribution, (5) design of siRNA molecules, (6) chemical modification and bioconjugation, (7) complex formation with lipids and polymers, (8) encapsulation into lipid particles, and (9) target specificity for enhanced therapeutic effectiveness. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)431-456
Number of pages26
Issue number4
StatePublished - Apr 2007
Externally publishedYes


  • Bioconjugation
  • Chemical modification
  • Complex formation
  • RNA interference
  • Small interfering RNA

ASJC Scopus subject areas

  • Molecular Biology


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