EMAIL THIS PAGE TO A FRIEND

Molecular therapy : the journal of the American Society of Gene Therapy

Adenoassociated virus serotype 9-mediated gene therapy for x-linked adrenoleukodystrophy.


PMID 25592337

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder caused by mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding cassette transporter (ABCD1) responsible for transport of CoA-activated very long-chain fatty acids (VLCFA) into the peroxisome for degradation. We used recombinant adenoassociated virus serotype 9 (rAAV9) vector for delivery of the human ABCD1 gene (ABCD1) to mouse central nervous system (CNS). In vitro, efficient delivery of ABCD1 gene was achieved in primary mixed brain glial cells from Abcd1-/- mice as well as X-ALD patient fibroblasts. Importantly, human ABCD1 localized to the peroxisome, and AAV-ABCD1 transduction showed a dose-dependent effect in reducing VLCFA. In vivo, AAV9-ABCD1 was delivered to Abcd1-/- mouse CNS by either stereotactic intracerebroventricular (ICV) or intravenous (IV) injections. Astrocytes, microglia and neurons were the major target cell types following ICV injection, while IV injection also delivered to microvascular endothelial cells and oligodendrocytes. IV injection also yielded high transduction of the adrenal gland. Importantly, IV injection of AAV9-ABCD1 reduced VLCFA in mouse brain and spinal cord. We conclude that AAV9-mediated ABCD1 gene transfer is able to reach target cells in the nervous system and adrenal gland as well as reduce VLCFA in culture and a mouse model of X-ALD.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB2500012
Anti-ABCD1 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB4500824
Anti-ABCD1 antibody produced in rabbit, affinity isolated antibody
HPA049234
Anti-AIF1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
AV32753
Anti-OLIG2 (AB1) antibody produced in rabbit, affinity isolated antibody
AV31464
Anti-OLIG2 (AB2) antibody produced in rabbit, affinity isolated antibody
AV32752
Anti-OLIG2 (AB3) antibody produced in rabbit, affinity isolated antibody
SAB1412293
ANTI-OLIG2 antibody produced in mouse, clone 2A8, purified immunoglobulin, buffered aqueous solution
SAB1412294
ANTI-OLIG2 antibody produced in mouse, clone 2B11, purified immunoglobulin, buffered aqueous solution
HPA003254
Anti-OLIG2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
WH0000215M1 Monoclonal Anti-ABCD1 antibody produced in mouse, clone 4B5, purified immunoglobulin, buffered aqueous solution
WH0000199M1
Monoclonal Anti-AIF1 antibody produced in mouse, clone 2A2-B6, purified immunoglobulin, buffered aqueous solution
WH0010215M2
Monoclonal Anti-OLIG2 antibody produced in mouse, clone 3D7, purified immunoglobulin, buffered aqueous solution
SAB1404798
Monoclonal Anti-OLIG2 antibody produced in mouse, clone 3C9, purified immunoglobulin, buffered aqueous solution
SAB5300407
Monoclonal Anti-OLIG2 antibody produced in mouse, clone 1G11, ascites fluid