title: Oligonucleotide delivery: a patent review (2010 - 2013).
abstract: BACKGROUND
  The use of aptamers, antisense technology and RNA interference has allowed nucleic acids to be considered as promising alternatives to classical drugs. However, nucleic acids face several obstacles in the creation of effective nucleic acid drugs. The development of these approaches has strengthened the pipeline with an increasing number of these therapies in clinical trials.
  
  
  METHODS
  This review covers research and patent literature from the last three years, focusing on the development of safe and effective non-viral drug delivery systems for the treatment of diseases such as cancer or genetic disorders by using oligonucleotides.
  
  
  CONCLUSIONS
  The therapeutic applications of oligonucleotides have overcome multiple obstacles, especially in biodistribution and cellular internalization. Cationic lipids are the most used vehicles for the preparation of novel formulations. Combinatorial libraries of these compounds and the use of solid lipid nanoparticles carrying these synthetic cationic lipids (cholesterol and PEG) have enhanced cellular uptake and biocompatibility of nucleic acids. Besides this extensive use, synthesis of oligonucleotides covalently linked to lipids has also emerged as a promising alternative to formulations. The use of peptides alone or in combination with lipids is an expanding field for oligonucleotide delivery. Polymeric platforms are also good candidates as they showed improved cellular uptake, biodegradability, biocompatibility and the possibility of incorporating several components, such as ligands for receptor-mediated endocytosis and molecules, to facilitate endosomal escape. Finally, nanomaterials may also play an important role in the future. The last developments showed improvement in in vivo efficacy, thus gaining a foothold in therapeutics.
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), and Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Department of Chemical and Biomolecular Nanotechnology , Jordi Girona 18-26, 08034 Barcelona , Spain +34 934006145 ; +34 932045904 ; recgma@cid.csic.es.
authors.forename: Santiago
authors.initials: S
authors.lastname: Grijalvo
authors.forename: Anna
authors.initials: A
authors.lastname: Aviñó
authors.forename: Ramon
authors.initials: R
authors.lastname: Eritja
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D006801:Humans; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000627:therapeutic use; D010330:Patents as Topic; D034622:RNA Interference
chemical_list: D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense
keywords: RNA interference; antisense; aptamers; cell penetration peptides; drug delivery; liposomes; nanoparticles; oligonucleotides; polymers; small interference RNA