title: Technologies for investigating the physiological barriers to efficient lipid nanoparticle-siRNA delivery.
abstract: 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.
authors.affiliation: Department of RNA Therapeutics, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania, USA. bin_shi@merck.com
authors.forename: Bin
authors.initials: B
authors.lastname: Shi
authors.forename: Marc
authors.initials: M
authors.lastname: Abrams
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D011992:Endosomes / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D060888:Real-Time Polymerase Chain Reaction; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D008055:Lipids; D034741:RNA, Small Interfering
keywords: LNP; QWBA; RISC; biodistribution; delivery; endosomal escape; immunofluorescence staining; intravital imaging; lipid nanoparticle; siRNA; stem-loop PCR