title: Enhancing the pharmacokinetic/pharmacodynamic properties of therapeutic nucleotides using lipid nanoparticle systems.
abstract: Although activity has been reported in vivo, free nucleic acid-based drugs are rapidly degraded and cleared following systemic administration. To address these challenges and improve the potency and bioavailability of genetic drugs, significant efforts have been made to develop effective delivery systems of which lipid nanoparticles (LNP) represent the most advanced technology currently available. In this review, we will describe and discuss the improvements to the pharmacokinetic and pharmacodynamic properties of nucleic acid-based drugs mediated by LNP delivery. It is envisioned that the significant improvements in potency and safety, largely driven by the development of LNP encapsulated siRNA drugs, will be translatable to other types of genetic drugs and enable the rapid development of potent molecular tools and drugs.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3, Canada.|Acuitas Therapeutics Inc., 2389 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
authors.forename: Paulo J C
authors.initials: PJ
authors.lastname: Lin
authors.affiliation: Department of Biochemistry & Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3, Canada.|Acuitas Therapeutics Inc., 2389 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
authors.forename: Ying K
authors.initials: YK
authors.lastname: Tam
mesh_terms: D000818:Animals; D021881:DNA, Catalytic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D035683:MicroRNAs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D009711:Nucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D016337:RNA, Catalytic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D021881:DNA, Catalytic; D004337:Drug Carriers; D008055:Lipids; D035683:MicroRNAs; D009711:Nucleotides; D016337:RNA, Catalytic; D034741:RNA, Small Interfering