title: Recent advances in characterization of nonviral vectors for delivery of nucleic acids: impact on their biological performance.
abstract: BACKGROUND
  Nucleic acid delivery is a complex process that requires transport across numerous extracellular and intracellular barriers, whose impact is often neglected during optimization studies. As such, the development of nonviral vectors for efficient delivery would benefit from an understanding of how these barriers relate to the physicochemical properties of lipoplexes and polyplexes.
  
  
  METHODS
  This review focuses on the evaluation of parameters associated with barriers to delivery such as blood and immune cells compatibility which, as a collective, may serve as a useful prescreening tool for the advancement of nonviral vectors in vivo. An outline of the most relevant rationally developed polyplexes and lipoplexes for clinical application is also given.
  
  
  CONCLUSIONS
  The evaluation of scientifically recognized parameters enabled the identification of systemic delivered nonviral vectors' behavior while in blood as one of the key determinants of vectors function and activity both in vitro and in vivo. This multiparametric approach complements the use of in vitro efficacy results alone for prescreening and improves in vitro-in vivo translation by minimizing false negatives. Further, it can aid in the identification of meaningful structure-function-activity relationships, improve the in vitro screening process of nonviral vectors before in vivo use and facilitate the future development of potent and safe nonviral vectors.
authors.affiliation: Group Genetics of Cognitive Dysfunction, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto , Rua do Campo Alegre, 4150-180, Porto , Portugal.
authors.forename: Claudia
authors.initials: C
authors.lastname: Oliveira
authors.forename: Isabel
authors.initials: I
authors.lastname: Silveira
authors.forename: Francisco
authors.initials: F
authors.lastname: Veiga
authors.forename: António J
authors.initials: AJ
authors.lastname: Ribeiro
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry* / Q000493:pharmacokinetics*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry* / Q000493:pharmacokinetics*; D006461:Hemolysis / Q000187:drug effects; D006648:Histocompatibility / Q000276:immunology; D055666:Lipopeptides / Q000737:chemistry / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000737:chemistry; D009696:Nucleic Acids / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D055666:Lipopeptides; D009696:Nucleic Acids; D011108:Polymers
keywords: biodistribution; immunocompatibility; nonviral vector; nucleic acid delivery; structure–activity relationship