Gene delivery of the therapeutic polypeptide erythropoietin to primary brain capillary endothelial cells for protein secretion

Publikation: Bidrag til bog/antologi/rapport/konference proceedingKonferenceabstrakt i proceedingForskningpeer review

Resumé

The potential for treatment of chronic disorders affecting the CNS is complicated by the inability of several drugs to cross the blood-brain barrier (BBB). None-viral gene therapy applied to brain capillary endothelial cells (BCECs) denotes a novel approach to overcome the restraints in this passage, as turning BCECs into recombinant protein factories by transfection could result in protein secretion into the brain. The non-mitotic BCECs might, however, not be very susceptible to non-viral gene therapy in vivo, since this strategy is believed to be dependent on active cell division. We have, however, recently shown that non-viral gene therapy to non-mitotic BCECs cultured in an in-vitro BBB model was possible without disrupting the barrier properties of the BCECs, and that this was as effective as transfection of dividing BCECs. The transfection efficiency is, however, low, questioning the possible effect of this protein delivery strategy in vivo. The aim of the present study was, therefore, to investigate the possibility of increasing the transfection efficiency using non-viral gene carriers, with the hope of increase the recombinant protein synthesis of erythropoietin, a protein recognized for its neuroprotective potential, from the BCECs. Our study opens for knowledge on, how non-viral gene therapy to BCECs can lead to protein secretion with the perspective of enabling therapeutic proteins to target neurons inside the CNS otherwise inhibited to access due to the restraints of the BBB. This therapeutic strategy could be beneficial in treatment of inherited diseases and classical neurodegenerative disorders.
OriginalsprogEngelsk
TitelFinal Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark
ForlagUniversity of Copenhagen
Publikationsdato2016
Sider25
ArtikelnummerO-5
StatusUdgivet - 2016
Begivenhed19th International Symposium on Signal Transduction at the Blood-Brain Barriers - København, Danmark
Varighed: 14 sep. 201616 sep. 2016

Konference

Konference19th International Symposium on Signal Transduction at the Blood-Brain Barriers
LandDanmark
ByKøbenhavn
Periode14/09/201616/09/2016

Bibliografisk note

Oral Presentation

Citer dette

Larsen, A. B., & Moos, T. (2016). Gene delivery of the therapeutic polypeptide erythropoietin to primary brain capillary endothelial cells for protein secretion. I Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark (s. 25). [O-5] University of Copenhagen.
Larsen, Annette Burkhart ; Moos, Torben. / Gene delivery of the therapeutic polypeptide erythropoietin to primary brain capillary endothelial cells for protein secretion. Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark. University of Copenhagen, 2016. s. 25
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abstract = "The potential for treatment of chronic disorders affecting the CNS is complicated by the inability of several drugs to cross the blood-brain barrier (BBB). None-viral gene therapy applied to brain capillary endothelial cells (BCECs) denotes a novel approach to overcome the restraints in this passage, as turning BCECs into recombinant protein factories by transfection could result in protein secretion into the brain. The non-mitotic BCECs might, however, not be very susceptible to non-viral gene therapy in vivo, since this strategy is believed to be dependent on active cell division. We have, however, recently shown that non-viral gene therapy to non-mitotic BCECs cultured in an in-vitro BBB model was possible without disrupting the barrier properties of the BCECs, and that this was as effective as transfection of dividing BCECs. The transfection efficiency is, however, low, questioning the possible effect of this protein delivery strategy in vivo. The aim of the present study was, therefore, to investigate the possibility of increasing the transfection efficiency using non-viral gene carriers, with the hope of increase the recombinant protein synthesis of erythropoietin, a protein recognized for its neuroprotective potential, from the BCECs. Our study opens for knowledge on, how non-viral gene therapy to BCECs can lead to protein secretion with the perspective of enabling therapeutic proteins to target neurons inside the CNS otherwise inhibited to access due to the restraints of the BBB. This therapeutic strategy could be beneficial in treatment of inherited diseases and classical neurodegenerative disorders.",
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Larsen, AB & Moos, T 2016, Gene delivery of the therapeutic polypeptide erythropoietin to primary brain capillary endothelial cells for protein secretion. i Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark., O-5, University of Copenhagen, s. 25, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, København, Danmark, 14/09/2016.

Gene delivery of the therapeutic polypeptide erythropoietin to primary brain capillary endothelial cells for protein secretion. / Larsen, Annette Burkhart; Moos, Torben.

Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark. University of Copenhagen, 2016. s. 25 O-5.

Publikation: Bidrag til bog/antologi/rapport/konference proceedingKonferenceabstrakt i proceedingForskningpeer review

TY - ABST

T1 - Gene delivery of the therapeutic polypeptide erythropoietin to primary brain capillary endothelial cells for protein secretion

AU - Larsen, Annette Burkhart

AU - Moos, Torben

N1 - Oral Presentation

PY - 2016

Y1 - 2016

N2 - The potential for treatment of chronic disorders affecting the CNS is complicated by the inability of several drugs to cross the blood-brain barrier (BBB). None-viral gene therapy applied to brain capillary endothelial cells (BCECs) denotes a novel approach to overcome the restraints in this passage, as turning BCECs into recombinant protein factories by transfection could result in protein secretion into the brain. The non-mitotic BCECs might, however, not be very susceptible to non-viral gene therapy in vivo, since this strategy is believed to be dependent on active cell division. We have, however, recently shown that non-viral gene therapy to non-mitotic BCECs cultured in an in-vitro BBB model was possible without disrupting the barrier properties of the BCECs, and that this was as effective as transfection of dividing BCECs. The transfection efficiency is, however, low, questioning the possible effect of this protein delivery strategy in vivo. The aim of the present study was, therefore, to investigate the possibility of increasing the transfection efficiency using non-viral gene carriers, with the hope of increase the recombinant protein synthesis of erythropoietin, a protein recognized for its neuroprotective potential, from the BCECs. Our study opens for knowledge on, how non-viral gene therapy to BCECs can lead to protein secretion with the perspective of enabling therapeutic proteins to target neurons inside the CNS otherwise inhibited to access due to the restraints of the BBB. This therapeutic strategy could be beneficial in treatment of inherited diseases and classical neurodegenerative disorders.

AB - The potential for treatment of chronic disorders affecting the CNS is complicated by the inability of several drugs to cross the blood-brain barrier (BBB). None-viral gene therapy applied to brain capillary endothelial cells (BCECs) denotes a novel approach to overcome the restraints in this passage, as turning BCECs into recombinant protein factories by transfection could result in protein secretion into the brain. The non-mitotic BCECs might, however, not be very susceptible to non-viral gene therapy in vivo, since this strategy is believed to be dependent on active cell division. We have, however, recently shown that non-viral gene therapy to non-mitotic BCECs cultured in an in-vitro BBB model was possible without disrupting the barrier properties of the BCECs, and that this was as effective as transfection of dividing BCECs. The transfection efficiency is, however, low, questioning the possible effect of this protein delivery strategy in vivo. The aim of the present study was, therefore, to investigate the possibility of increasing the transfection efficiency using non-viral gene carriers, with the hope of increase the recombinant protein synthesis of erythropoietin, a protein recognized for its neuroprotective potential, from the BCECs. Our study opens for knowledge on, how non-viral gene therapy to BCECs can lead to protein secretion with the perspective of enabling therapeutic proteins to target neurons inside the CNS otherwise inhibited to access due to the restraints of the BBB. This therapeutic strategy could be beneficial in treatment of inherited diseases and classical neurodegenerative disorders.

M3 - Conference abstract in proceeding

SP - 25

BT - Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark

PB - University of Copenhagen

ER -

Larsen AB, Moos T. Gene delivery of the therapeutic polypeptide erythropoietin to primary brain capillary endothelial cells for protein secretion. I Final Programme, 19th International Symposium on Signal Transduction at the Blood-Brain Barriers, 14-16 September 2016, Copenhagen, Denmark. University of Copenhagen. 2016. s. 25. O-5