Targeted delivery of antisense oligonucleotides and siRNAs into mammalian cells.
RNA interference (RNAi) is a natural mechanism for gene silencing that can be harnessed for the development of RNA-based drugs. Although synthetic small interfering RNA (siRNAs) can be delivered in vitro to virtually all cell types using lipid-based transfection agents or electroporation, efficient strategies for achieving either systemic or targeted delivery remains one of the major in vivo challenges. Among the targeting strategies, receptor-targeted delivery provides an innovative strategy to selectively direct therapeutics to cancer cells. Receptor-binding peptides can be incorporated into gene-delivery vesicles or directly conjugated to siRNAs in the hope of promoting their localization in target cells expressing the cognate receptors. This chapter discusses the current status of siRNA-targeting strategies using either peptides identified through iterative screening of random peptide phage libraries or naturally occurring peptides. Also, transcriptional targeting strategies and detailed protocols for the selection of cancer cell-binding peptide from random peptide libraries are described.
Sioud
Mouldy
M
Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, University of Oslo, Norway.
D001943:Breast Neoplasms / Q000188:drug therapy*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D005260:Female; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D019151:Peptide Library; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016376:Oligonucleotides, Antisense; D019151:Peptide Library; D034741:RNA, Small Interfering