title: Complexity in the therapeutic delivery of RNAi medicines: an analytical challenge.
abstract: BACKGROUND
  Nucleic acids have witnessed a dramatic acceleration in their therapeutic exploitation and currently represent a growing number of applications in drug development pipelines. However, a more wide-spread development of therapeutics based on nucleic acids is restricted by their poor chemical and enzymatic stability in vivo, lack of cellular uptake and insufficient capability to reach intracellular targets.
  
  
  METHODS
  Advanced formulation of nucleic acids in nano-sized carriers may help unlocking their potential as therapeutic agents. Nano-sized matters own specific features responsible for inducing characteristic interactions with biological molecules and tissues. These properties enable for the enhancement of the nano-formulation's therapeutic efficacy, but on the other hand, the nanomatters interactions in biological fluids are also responsible for adverse effects. The purpose of this review is to reflect on the complexity in the therapeutic delivery of RNA interference-based drugs emerging from the recent clinical experiences and report the actual technological and analytical advances introduced to solve it.
  
  
  CONCLUSIONS
  The complexity in the therapeutic delivery of nucleic acids and the heterogeneity of side effects make the interpretation of the therapeutic outcome difficult. Hence the development of analytical approaches applicable in the field of nucleic acid delivery is becoming a major challenge.
authors.affiliation: University of Copenhagen, Department of Pharmacy, Faculty of Health and Medical Sciences , Universitetsparken 2, Copenhagen, 2100-DK , Denmark +45 35 33 64 02 ; camilla.foged@sund.ku.dk.
authors.forename: Stefano
authors.initials: S
authors.lastname: Colombo
authors.forename: Xianghui
authors.initials: X
authors.lastname: Zeng
authors.forename: Héloïse
authors.initials: H
authors.lastname: Ragelle
authors.forename: Camilla
authors.initials: C
authors.lastname: Foged
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D006801:Humans; D009696:Nucleic Acids / Q000008:administration & dosage*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D009696:Nucleic Acids; D034741:RNA, Small Interfering
keywords: RNA interference; RNA interference therapeutics; delivery; nucleic acid delivery; small interfering RNA