Technologies for Investigating the Physiological Barriers to Efficient Lipid Nanoparticle–siRNA Delivery

• Published in: The journal of histochemistry and cytochemistry Vol. 61; no. 6; pp. 407 - 420
• Main Authors: Shi, Bin, Abrams, Marc
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.06.2013
• Subjects: Animals; Drug Carriers - chemistry; Drug Delivery Systems; Endosomes - metabolism; Fluorescent Antibody Technique; Humans; Lipids - chemistry; Nanoparticles - chemistry; Real-Time Polymerase Chain Reaction; Review; RNA, Small Interfering - administration & dosage; RNA, Small Interfering - chemistry; RNA, Small Interfering - pharmacokinetics; Tissue Distribution; RISC; delivery; lipid nanoparticle; biodistribution; QWBA; immunofluorescence staining; siRNA; endosomal escape; intravital imaging; LNP; stem-loop PCR
• ISSN: 0022-1554; 1551-5044
• DOI: 10.1369/0022155413484152

Small interfering RNA (siRNA) therapeutics have advanced from bench to clinical trials in recent years, along with new tools developed to enable detection of siRNA delivered at the organ, cell, and subcellular levels. Preclinical models of siRNA delivery have benefitted from methodologies such as stem-loop quantitative polymerase chain reaction, histological in situ immunofluorescent staining, endosomal escape assay, and RNA-induced silencing complex loading assay. These technologies have accelerated the detection and optimization of siRNA platforms to overcome the challenges associated with delivering therapeutic oligonucleotides to the cytosol of specific target cells. This review focuses on the methodologies and their application in the biodistribution of siRNA delivered by lipid nanoparticles.