title: Cell Penetrating Peptide Conjugated Chitosan for Enhanced Delivery of Nucleic Acid.
abstract: Gene therapy is an emerging therapeutic strategy for the cure or treatment of a spectrum of genetic disorders. Nevertheless, advances in gene therapy are immensely reliant upon design of an efficient gene carrier that can deliver genetic cargoes into the desired cell populations. Among various nonviral gene delivery systems, chitosan-based carriers have gained increasing attention because of their high cationic charge density, excellent biocompatibility, nearly nonexistent cytotoxicity, negligible immune response, and ideal ability to undergo chemical conjugation. However, a major shortcoming of chitosan-based carriers is their poor cellular uptake, leading to inadequate transfection efficiency. The intrinsic feature of cell penetrating peptides (CPPs) for transporting diverse cargoes into multiple cell and tissue types in a safe manner suggests that they can be conjugated to chitosan for improving its transfection efficiency. In this review, we briefly discuss CPPs and their classification, and also the major mechanisms contributing to the cellular uptake of CPPs and cargo conjugates. We also discuss immense improvements for the delivery of nucleic acids using CPP-conjugated chitosan-based carriers with special emphasis on plasmid DNA and small interfering RNA.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 308 Harvard Street S.E., Minneapolis, MN 55455, USA. blayek@umn.edu.
authors.forename: Buddhadev
authors.initials: B
authors.lastname: Layek
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, North Dakota State University, Fargo, ND 58105, USA. lindsey.will@ndsu.edu.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Lipp
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, North Dakota State University, Fargo, ND 58105, USA. jagdish.singh@ndsu.edu.
authors.forename: Jagdish
authors.initials: J
authors.lastname: Singh
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism; D048271:Chitosan / Q000031:analogs & derivatives* / Q000378:metabolism; D004705:Endocytosis; D018014:Gene Transfer Techniques; D006801:Humans; D008958:Models, Molecular; D009696:Nucleic Acids / Q000008:administration & dosage* / Q000235:genetics; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics
chemical_list: D057846:Cell-Penetrating Peptides; D009696:Nucleic Acids; D034741:RNA, Small Interfering; D048271:Chitosan
keywords: cell penetrating peptides (CPPs); cellular uptake; chitosan; gene delivery; nonviral vector; transfection