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 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.

journal_name

EMBO Mol Med

journal_title

EMBO molecular medicine

authors

Körbelin J,Dogbevia G,Michelfelder S,Ridder DA,Hunger A,Wenzel J,Seismann H,Lampe M,Bannach J,Pasparakis M,Kleinschmidt JA,Schwaninger M,Trepel M

doi

10.15252/emmm.201506078

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

609-25

issue

6

eissn

1757-4676

issn

1757-4684

pii

emmm.201506078

journal_volume

8

pub_type

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