Angubindin-1 opens the blood-brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system

Journal of Controlled Release : Official Journal of the Controlled Release Society
Satoshi ZeniyaTakanori Yokota

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

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
Jul 3, 2020·Chemical & Pharmaceutical Bulletin·Koki OgawaShigeru Kawakami
Oct 12, 2019·Nature Reviews. Cancer·Costas D ArvanitisRakesh K Jain
Jun 4, 2019·Frontiers in Pharmacology·Svetlana Miroshnichenko, Olga Patutina
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 23, 2020·Drug Discovery Today·Yosuke HashimotoMasuo Kondoh
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

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.