Gene therapy targeting the blood-brain barrier
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Gene therapy targeting the blood-brain barrier. / Körbelin, Jakob; Arrulo, Adriana; Schwaninger, Markus.
In: VITAM HORM, Vol. 126, 2024, p. 191-217.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - Gene therapy targeting the blood-brain barrier
AU - Körbelin, Jakob
AU - Arrulo, Adriana
AU - Schwaninger, Markus
N1 - Copyright © 2024. Published by Elsevier Inc.
PY - 2024
Y1 - 2024
N2 - Endothelial cells are the building blocks of vessels in the central nervous system (CNS) and form the blood-brain barrier (BBB). An intact BBB limits permeation of large hydrophilic molecules into the CNS. Thus, the healthy BBB is a major obstacle for the treatment of CNS disorders with antibodies, recombinant proteins or viral vectors. Several strategies have been devised to overcome the barrier. A key principle often consists in attaching the therapeutic compound to a ligand of receptors expressed on the BBB, for example, the transferrin receptor (TfR). The fusion molecule will bind to TfR on the luminal side of brain endothelial cells, pass the endothelial layer by transcytosis and be delivered to the brain parenchyma. However, attempts to endow therapeutic compounds with the ability to cross the BBB can be difficult to implement. An alternative and possibly more straight-forward approach is to produce therapeutic proteins in the endothelial cells that form the barrier. These cells are accessible from blood circulation and have a large interface with the brain parenchyma. They may be an ideal production site for therapeutic protein and afford direct supply to the CNS.
AB - Endothelial cells are the building blocks of vessels in the central nervous system (CNS) and form the blood-brain barrier (BBB). An intact BBB limits permeation of large hydrophilic molecules into the CNS. Thus, the healthy BBB is a major obstacle for the treatment of CNS disorders with antibodies, recombinant proteins or viral vectors. Several strategies have been devised to overcome the barrier. A key principle often consists in attaching the therapeutic compound to a ligand of receptors expressed on the BBB, for example, the transferrin receptor (TfR). The fusion molecule will bind to TfR on the luminal side of brain endothelial cells, pass the endothelial layer by transcytosis and be delivered to the brain parenchyma. However, attempts to endow therapeutic compounds with the ability to cross the BBB can be difficult to implement. An alternative and possibly more straight-forward approach is to produce therapeutic proteins in the endothelial cells that form the barrier. These cells are accessible from blood circulation and have a large interface with the brain parenchyma. They may be an ideal production site for therapeutic protein and afford direct supply to the CNS.
KW - Blood-Brain Barrier/metabolism
KW - Humans
KW - Genetic Therapy/methods
KW - Animals
KW - Endothelial Cells/metabolism
KW - Receptors, Transferrin/metabolism
U2 - 10.1016/bs.vh.2024.03.001
DO - 10.1016/bs.vh.2024.03.001
M3 - SCORING: Review article
C2 - 39029973
VL - 126
SP - 191
EP - 217
JO - VITAM HORM
JF - VITAM HORM
SN - 0083-6729
ER -