title: Cell-penetrating peptides for the delivery of nucleic acids.
abstract: BACKGROUND
  Different gene therapy approaches have gained extensive interest lately and, after many initial hurdles, several promising approaches have reached to the clinics. Successful implementation of gene therapy is heavily relying on finding efficient measures to deliver genetic material to cells. Recently, non-viral delivery of nucleic acids and their analogs has gained significant interest. Among non-viral vectors, cell-penetrating peptides (CPPs) have been extensively used for the delivery of nucleic acids both in vitro and in vivo.
  
  
  METHODS
  In this review we will discuss recent advances of CPP-mediated delivery of nucleic acid-based cargo, concentrating on the delivery of plasmid DNA, splice-correcting ONs, and small-interfering RNAs.
  
  
  CONCLUSIONS
  CPPs have proved their potential as carriers for nucleic acids. However, similarly to other non-viral vectors, CPPs require further development, as efficient systemic delivery is still seldom achieved. To achieve this, CPPs should be modified with entities that would allow better endosomal escape, targeting of specific tissues and cells, and shielding agents that increase the half-life of the vehicles. Finally, to understand the clinical potential of CPPs, they require more thorough investigations in clinically relevant disease models and in pre-clinical and clinical studies.
authors.affiliation: University of Tartu, Institute of Technology, Laboratory of Molecular Biotechnology, Tartu, Estonia. tlehto@ut.ee
authors.forename: Taavi
authors.initials: T
authors.lastname: Lehto
authors.forename: Kaido
authors.initials: K
authors.lastname: Kurrikoff
authors.forename: Ülo
authors.initials: Ü
authors.lastname: Langel
mesh_terms: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009696:Nucleic Acids / Q000008:administration & dosage*; D009841:Oligonucleotides / Q000008:administration & dosage; D010957:Plasmids; D034741:RNA, Small Interfering / Q000008:administration & dosage
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D009696:Nucleic Acids; D009841:Oligonucleotides; D034741:RNA, Small Interfering