Abstract
Within the field of RNA therapeutics, antisense oligonucleotide-based therapeutics are a potentially powerful means of treating intractable diseases. However, if these therapeutics are used for the treatment of neurological disorders, safe yet efficient methods of delivering antisense oligonucleotides across the blood-brain barrier to the central nervous system must be developed. Here, we examined the use of angubindin-1, a binder to the tricellular tight junction, to modulate paracellular transport between brain microvascular endothelial cells in the blood-brain barrier for the delivery of antisense oligonucleotides to the central nervous system. This proof-of-concept study demonstrated that intravenously injected angubindin-1 increased the permeability of the blood-brain barrier and enabled transient delivery of subsequently administered antisense oligonucleotides into the mouse brain and spinal cord, leading to silencing of a target RNA without any overt adverse effects. We also found that two bicellular tight junction modulators did not produce such a silencing effect, suggesting that the tricellular tight junction is likely a better target for the delivery of antisense oligonucleotides than the bicellular tight junction. O...Continue Reading
Citations
May 30, 2019·Pharmaceutics·Alessandro ParodiAndrey A Zamyatnin
Aug 21, 2019·International Journal of Molecular Sciences·Yosuke HashimotoMasuo Kondoh
Nov 19, 2019·Brain : a Journal of Neurology·Ana C SilvaLuis Pereira de Almeida
Nov 20, 2019·Expert Opinion on Drug Discovery·Kenneth K W ToWilliam C S Cho
Nov 30, 2019·Tissue Barriers·Takumi KonnoTakashi Kojima
Oct 28, 2019·Histochemistry and Cell Biology·Takuro KyunoTakashi Kojima
Jul 3, 2020·Chemical & Pharmaceutical Bulletin·Koki OgawaShigeru Kawakami
Sep 17, 2020·Expert Opinion on Drug Delivery·Sam MaherDavid J Brayden
Oct 12, 2019·Nature Reviews. Cancer·Costas D ArvanitisRakesh K Jain
Jun 4, 2019·Frontiers in Pharmacology·Svetlana Miroshnichenko, Olga Patutina
Oct 10, 2018·Toxins·Masahiro NagahamaKeiko Kobayashi
Dec 10, 2019·Biochimica Et Biophysica Acta. Biomembranes·Tomohito Higashi, Hideki Chiba
Feb 23, 2021·Advanced Drug Delivery Reviews·Joël BrunnerGerrit Borchard
May 1, 2020·Biochimica Et Biophysica Acta. Biomembranes·Yosuke Hashimoto, Matthew Campbell
Mar 27, 2021·International Journal of Biological Macromolecules·Cameron WellsLezanne Ooi
Apr 30, 2021·Journal of Cell Science·Mariana Castro DiasBritta Engelhardt
May 1, 2021·Nucleic Acids Research·Ken AsadaTakanori Yokota
May 23, 2020·Drug Discovery Today·Yosuke HashimotoMasuo Kondoh
Aug 14, 2021·Nature Biotechnology·Tetsuya NagataTakanori Yokota
Aug 18, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Takayuki KohnoTakashi Kojima
Aug 28, 2021·International Journal of Molecular Sciences·Kizuku OhwadaTakashi Kojima
Nov 28, 2021·Pharmaceutics·Rory WhelanAndrew J S Knox