Ligand-targeted delivery of small interfering RNAs to malignant cells and tissues

Mini Thomas, Sumith A. Kularatne, Longwu Qi, Paul Kleindl, Christopher P. Leamon, Michael J. Hansen, Philip S. Low

Research output: Chapter in Book/Report/Conference proceedingConference contribution

69 Scopus citations


Potential clinical applications of small interfering RNA (siRNA) are hampered primarily by delivery issues. We have successfully addressed the delivery problems associated with off-site targeting of highly toxic chemotherapeutic agents by attaching the drugs to tumor-specific ligands that will carry the attached cargo into the desired cancer cell. Indeed, several such tumor-targeted drugs are currently undergoing human clinical trials. We now show that efficient targeting of siRNA to malignant cells and tissues can be achieved by covalent conjugation of small-molecular-weight, high-affinity ligands, such as folic acid and DUPA (2-[3-(1, 3-dicarboxy propyl)-ureido] pentanedioic acid), to siRNA. The former ligand binds a folate receptor that is overexpressed on a variety of cancers, whereas the latter ligand binds to prostate-specific membrane antigen that is overexpressed specifically on prostate cancers and the neovasculature of all solid tumors. Using these ligands, we show remarkable receptor-mediated targeting of siRNA to cancer tissues in vitro and in vivo.

Original languageEnglish (US)
Title of host publicationOligonucleotide Therapeutics Fourth Annual Meeting
PublisherBlackwell Publishing Inc.
Number of pages8
ISBN (Print)9781573317580
StatePublished - Sep 1 2009

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • DUPA
  • Endosomal escape
  • Folate receptor
  • PSMA
  • SiRNA
  • SiRNA targeting

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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