Gene therapy targeting the blood-brain barrier

Jakob Körbelin; Adriana Arrulo; Markus Schwaninger

doi:10.1016/bs.vh.2024.03.001

Gene therapy targeting the blood-brain barrier

Standard

Gene therapy targeting the blood-brain barrier. / Körbelin, Jakob; Arrulo, Adriana; Schwaninger, Markus.

in: VITAM HORM, Jahrgang 126, 2024, S. 191-217.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung

Harvard

Körbelin, J, Arrulo, A & Schwaninger, M 2024, 'Gene therapy targeting the blood-brain barrier', VITAM HORM, Jg. 126, S. 191-217. https://doi.org/10.1016/bs.vh.2024.03.001

APA

Körbelin, J., Arrulo, A., & Schwaninger, M. (2024). Gene therapy targeting the blood-brain barrier. VITAM HORM, 126, 191-217. https://doi.org/10.1016/bs.vh.2024.03.001

Vancouver

Körbelin J, Arrulo A, Schwaninger M. Gene therapy targeting the blood-brain barrier. VITAM HORM. 2024;126:191-217. https://doi.org/10.1016/bs.vh.2024.03.001

Bibtex

@article{76ffd26b943140c983f254c7990d962e,

title = "Gene therapy targeting the blood-brain barrier",

abstract = "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.",

keywords = "Blood-Brain Barrier/metabolism, Humans, Genetic Therapy/methods, Animals, Endothelial Cells/metabolism, Receptors, Transferrin/metabolism",

author = "Jakob K{\"o}rbelin and Adriana Arrulo and Markus Schwaninger",

note = "Copyright {\textcopyright} 2024. Published by Elsevier Inc.",

year = "2024",

doi = "10.1016/bs.vh.2024.03.001",

language = "English",

volume = "126",

pages = "191--217",

journal = "VITAM HORM",

issn = "0083-6729",

publisher = "Academic Press Inc.",

}

RIS

TY - JOUR

T1 - Gene therapy targeting the blood-brain barrier

AU - Körbelin, Jakob

AU - Arrulo, Adriana

AU - Schwaninger, Markus

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 -