A brain microvasculature endothelial cell‐specific viral vector with the potential to treat neurovascular and neurological diseases
Abstract Gene therapy critically relies on vectors that combine high transduction efficiency with a high degree of target specificity and that can be administered through a safe intravenous route. The lack of suitable vectors, especially for gene therapy of brain disorders, represents a major obstac...
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-04-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201506078 |
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| author | Jakob Körbelin Godwin Dogbevia Stefan Michelfelder Dirk A Ridder Agnes Hunger Jan Wenzel Henning Seismann Melanie Lampe Jacqueline Bannach Manolis Pasparakis Jürgen A Kleinschmidt Markus Schwaninger Martin Trepel |
| author_facet | Jakob Körbelin Godwin Dogbevia Stefan Michelfelder Dirk A Ridder Agnes Hunger Jan Wenzel Henning Seismann Melanie Lampe Jacqueline Bannach Manolis Pasparakis Jürgen A Kleinschmidt Markus Schwaninger Martin Trepel |
| author_sort | Jakob Körbelin |
| collection | DOAJ |
| description | Abstract Gene therapy critically relies on vectors that combine high transduction efficiency with a high degree of target specificity and that can be administered through a safe intravenous route. The lack of suitable vectors, especially for gene therapy of brain disorders, represents a major obstacle. Therefore, we applied an in vivo screening system of random ligand libraries displayed on adeno‐associated viral capsids to select brain‐targeted vectors for the treatment of neurovascular diseases. We identified a capsid variant showing an unprecedented degree of specificity and long‐lasting transduction efficiency for brain microvasculature endothelial cells as the primary target of selection. A therapeutic vector based on this selected viral capsid was used to markedly attenuate the severe cerebrovascular pathology of mice with incontinentia pigmenti after a single intravenous injection. Furthermore, the versatility of this selection system will make it possible to select ligands for additional in vivo targets without requiring previous identification of potential target‐specific receptors. |
| format | Article |
| id | doaj-art-b52f1692373e499a82e3aeb7fb5c9aef |
| institution | DOAJ |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-04-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-b52f1692373e499a82e3aeb7fb5c9aef2025-08-20T03:06:00ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-04-018660962510.15252/emmm.201506078A brain microvasculature endothelial cell‐specific viral vector with the potential to treat neurovascular and neurological diseasesJakob Körbelin0Godwin Dogbevia1Stefan Michelfelder2Dirk A Ridder3Agnes Hunger4Jan Wenzel5Henning Seismann6Melanie Lampe7Jacqueline Bannach8Manolis Pasparakis9Jürgen A Kleinschmidt10Markus Schwaninger11Martin Trepel12Hubertus Wald Cancer Center, Department of Oncology and Hematology, University Medical Center Hamburg‐EppendorfInstitute of Experimental and Clinical Pharmacology and Toxicology, University of LübeckHubertus Wald Cancer Center, Department of Oncology and Hematology, University Medical Center Hamburg‐EppendorfInstitute of Experimental and Clinical Pharmacology and Toxicology, University of LübeckHubertus Wald Cancer Center, Department of Oncology and Hematology, University Medical Center Hamburg‐EppendorfInstitute of Experimental and Clinical Pharmacology and Toxicology, University of LübeckHubertus Wald Cancer Center, Department of Oncology and Hematology, University Medical Center Hamburg‐EppendorfHubertus Wald Cancer Center, Department of Oncology and Hematology, University Medical Center Hamburg‐EppendorfInstitute of Experimental and Clinical Pharmacology and Toxicology, University of LübeckCologne Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD) and Centre for Molecular Medicine (CMMC), Institute for Genetics, University of CologneDepartment of Tumor Virology, German Cancer Research CenterInstitute of Experimental and Clinical Pharmacology and Toxicology, University of LübeckHubertus Wald Cancer Center, Department of Oncology and Hematology, University Medical Center Hamburg‐EppendorfAbstract Gene therapy critically relies on vectors that combine high transduction efficiency with a high degree of target specificity and that can be administered through a safe intravenous route. The lack of suitable vectors, especially for gene therapy of brain disorders, represents a major obstacle. Therefore, we applied an in vivo screening system of random ligand libraries displayed on adeno‐associated viral capsids to select brain‐targeted vectors for the treatment of neurovascular diseases. We identified a capsid variant showing an unprecedented degree of specificity and long‐lasting transduction efficiency for brain microvasculature endothelial cells as the primary target of selection. A therapeutic vector based on this selected viral capsid was used to markedly attenuate the severe cerebrovascular pathology of mice with incontinentia pigmenti after a single intravenous injection. Furthermore, the versatility of this selection system will make it possible to select ligands for additional in vivo targets without requiring previous identification of potential target‐specific receptors.https://doi.org/10.15252/emmm.201506078adeno‐associated virusbrain microvascular endothelial cellsgene therapyneurovascular diseases |
| spellingShingle | Jakob Körbelin Godwin Dogbevia Stefan Michelfelder Dirk A Ridder Agnes Hunger Jan Wenzel Henning Seismann Melanie Lampe Jacqueline Bannach Manolis Pasparakis Jürgen A Kleinschmidt Markus Schwaninger Martin Trepel A brain microvasculature endothelial cell‐specific viral vector with the potential to treat neurovascular and neurological diseases EMBO Molecular Medicine adeno‐associated virus brain microvascular endothelial cells gene therapy neurovascular diseases |
| title | A brain microvasculature endothelial cell‐specific viral vector with the potential to treat neurovascular and neurological diseases |
| title_full | A brain microvasculature endothelial cell‐specific viral vector with the potential to treat neurovascular and neurological diseases |
| title_fullStr | A brain microvasculature endothelial cell‐specific viral vector with the potential to treat neurovascular and neurological diseases |
| title_full_unstemmed | A brain microvasculature endothelial cell‐specific viral vector with the potential to treat neurovascular and neurological diseases |
| title_short | A brain microvasculature endothelial cell‐specific viral vector with the potential to treat neurovascular and neurological diseases |
| title_sort | brain microvasculature endothelial cell specific viral vector with the potential to treat neurovascular and neurological diseases |
| topic | adeno‐associated virus brain microvascular endothelial cells gene therapy neurovascular diseases |
| url | https://doi.org/10.15252/emmm.201506078 |
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