Serotype-dependent transduction efficiencies of recombinant adeno-associated viral vectors in monkey neocortex

被引：36

作者：

Gerits, Annelies ^{[1
]}

Vancraeyenest, Pascaline ^{[1
]}

Vreysen, Samme ^{[2
]}

Laramee, Marie-Eve ^{[2
]}

Michiels, Annelies ^{[3
,4
]}

Gijsbers, Rik ^{[4
,5
]}

Van den Haute, Chris ^{[3
,4
]}

Moons, Lieve ^{[6
]}

Debyser, Zeger ^{[5
]}

Baekelandt, Veerle ^{[3
]}

Arckens, Lutgarde ^{[2
]}

Vanduffel, Wim ^{[1
,7
,8
]}

机构：

[1] Katholieke Univ Leuven, Lab Neuro & Psychophysiol, Dept Neurosci, O&N2 Herestr 49 Bus 10-21, B-3000 Leuven, Belgium

[2] Katholieke Univ Leuven, Lab Neuroplast & Neuroprote, Fac Sci, B-3000 Leuven, Belgium

[3] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Dept Neurosci, B-3000 Leuven, Belgium

[4] Katholieke Univ Leuven, Leuven Viral Vector Core, B-3000 Leuven, Belgium

[5] Katholieke Univ Leuven, Lab Mol Virol & Gene Therapy, Dept Neurosci, B-3000 Flanders, Belgium

[6] Katholieke Univ Leuven, Lab Neural Circuit Dev & Regenerat, Fac Sci, B-3000 Leuven, Belgium

[7] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA

[8] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA

来源：

NEUROPHOTONICS | 2015年 / 2卷 / 03期

关键词：

promoters; histology; monkey; optogenetics; gene transfer; cell-specific expression; CENTRAL-NERVOUS-SYSTEM; NONHUMAN PRIMATE BRAIN; VIRUS AAV; LENTIVIRAL VECTORS; GENE-EXPRESSION; PROTEIN-KINASE; IN-VIVO; NEUROLOGICAL DISORDERS; TRANSGENE EXPRESSION; PARKINSONS-DISEASE;

D O I：

10.1117/1.NPh.2.3.031209

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Viral vector-mediated expression of genes (e. g., coding for opsins and designer receptors) has grown increasingly popular. Cell-type specific expression is achieved by altering viral vector tropism through cross-packaging or by cell-specific promoters driving gene expression. Detailed information about transduction properties of most recombinant adeno-associated viral vector (rAAV) serotypes in macaque cortex is gradually becoming available. Here, we compare transduction efficiencies and expression patterns of reporter genes in two macaque neocortical areas employing different rAAV serotypes and promoters. A short version of the calmodulin-kinase-II (CaMKIIa0.4) promoter resulted in reporter gene expression in cortical neurons for all tested rAAVs, albeit with different efficiencies for spread: rAAV2/5>>rAAV2/7>rAAV2/8>rAAV2/9>>rAAV2/1 and proportion of transduced cells: rAAV2/1>rAAV2/5>rAAV2/7= rAAV2/9>rAAV2/8. In contrast to rodent studies, the cytomegalovirus (CMV) promoter appeared least efficient in macaque cortex. The human synapsin-1 promoter preceded by the CMV enhancer (enhSyn1) produced homogeneous reporter gene expression across all layers, while two variants of the CaMKIIa promoter resulted in different laminar transduction patterns and cell specificities. Finally, differences in expression patterns were observed when the same viral vector was injected in two neocortical areas. Our results corroborate previous findings that reporter-gene expression patterns and efficiency of rAAV transduction depend on serotype, promoter, cortical layer, and area. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

引用

页数：17

共 82 条

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