Abstract

Short interfering RNAs (siRNAs) have emerged as a potent new class of therapeutics, which regulate gene expression through sequence-specific inhibition of mRNA translation. Human trials of siRNAs have highlighted the need for robust delivery and detection techniques that will enable the application of these therapeutics to increasingly complex disease and organ systems. Efforts to monitor the in vivo trafficking and efficacy of siRNAs have routinely involved bioluminescence imaging of naked siRNA molecules. More recently, siRNAs have been incorporated into a variety of molecular imaging probes to promote their detection with clinically relevant imaging modalities. Lipid-, polymer-, and nanoparticle-based siRNA delivery vehicles have proven effective in improving the stability, bioavailability, and target specificity of siRNAs following systemic administration in vivo. Additionally, these methods provide a platform to modify siRNAs with a variety of contrast agents and have enabled nuclear and magnetic resonance imaging of siRNA delivery in preclinical studies. These image-guided delivery approaches represent a crucial step in the transition of siRNA therapeutics to the clinic.