title: Non-Viral Nucleic Acid Delivery Strategies to the Central Nervous System.
abstract: With an increased prevalence and understanding of central nervous system (CNS) injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore thein vivochallenges hindering non-viral nucleic acid delivery to the CNS and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstratedin vivogene transfer to the CNS are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for CNS applications and will ultimately bring non-viral vectors closer to clinical application.
authors.affiliation: Department of Bioengineering and Molecular Engineering & Sciences Institute, University of Washington Seattle, WA, USA.
authors.forename: James-Kevin Y
authors.initials: JY
authors.lastname: Tan
authors.affiliation: Department of Bioengineering and Molecular Engineering & Sciences Institute, University of Washington Seattle, WA, USA.
authors.forename: Drew L
authors.initials: DL
authors.lastname: Sellers
authors.affiliation: Department of Bioengineering and Molecular Engineering & Sciences Institute, University of Washington Seattle, WA, USA.
authors.forename: Binhan
authors.initials: B
authors.lastname: Pham
authors.affiliation: Department of Bioengineering and Molecular Engineering & Sciences Institute, University of Washington Seattle, WA, USA.
authors.forename: Suzie H
authors.initials: SH
authors.lastname: Pun
authors.affiliation: Center for Neuroregenerative Medicine, Houston Methodist Research Institute Houston, TX, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Horner
keywords: central nervous system; delivery; in vivo; non-viral; nucleic acid