title: Serotype-dependent transduction efficiencies of recombinant adeno-associated viral vectors in monkey neocortex.
abstract: 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 crosspackaging 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 (CaMKIIα0.4) 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 CaMKIIα 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.
authors.affiliation: KU Leuven , Laboratory of Neuro- and Psychophysiology, Department of Neurosciences, O&N2 Herestraat 49 bus 10.21, 3000 Leuven, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Gerits
authors.affiliation: KU Leuven , Laboratory of Neuro- and Psychophysiology, Department of Neurosciences, O&N2 Herestraat 49 bus 10.21, 3000 Leuven, Belgium.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Vancraeyenest
authors.affiliation: KU Leuven , Laboratory of Neuroplasticity and Neuroproteomics, Faculty of Science, Naamsestraat 59, 3000 Leuven, Belgium.
authors.forename: Samme
authors.initials: S
authors.lastname: Vreysen
authors.affiliation: KU Leuven , Laboratory of Neuroplasticity and Neuroproteomics, Faculty of Science, Naamsestraat 59, 3000 Leuven, Belgium.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Laramée
authors.affiliation: KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Kapucijnenvoer 33, VCTB +5, 3000 Leuven, Belgium; KU Leuven, Leuven Viral Vector Core, Kapucijnenvoer 33, VCTB +5, 3000 Leuven, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Michiels
authors.affiliation: KU Leuven, Leuven Viral Vector Core, Kapucijnenvoer 33, VCTB +5, 3000 Leuven, Belgium; KU Leuven, Laboratory of Molecular Virology and Gene Therapy, Department of Neurosciences, Kapucijnenvoer 33, VCTB +5, 3000 Leuven, Flanders, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Gijsbers
authors.affiliation: KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Kapucijnenvoer 33, VCTB +5, 3000 Leuven, Belgium; KU Leuven, Leuven Viral Vector Core, Kapucijnenvoer 33, VCTB +5, 3000 Leuven, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Van den Haute
authors.affiliation: KU Leuven , Laboratory of Neural Circuit Development and Regeneration, Faculty of Science, Naamsestraat 61, 3000 Leuven, Belgium.
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.affiliation: KU Leuven , Laboratory of Molecular Virology and Gene Therapy, Department of Neurosciences, Kapucijnenvoer 33, VCTB +5, 3000 Leuven, Flanders, Belgium.
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.affiliation: KU Leuven , Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Kapucijnenvoer 33, VCTB +5, 3000 Leuven, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
authors.affiliation: KU Leuven , Laboratory of Neuroplasticity and Neuroproteomics, Faculty of Science, Naamsestraat 59, 3000 Leuven, Belgium.
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Arckens
authors.affiliation: KU Leuven, Laboratory of Neuro- and Psychophysiology, Department of Neurosciences, O&N2 Herestraat 49 bus 10.21, 3000 Leuven, Belgium; Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, 149 13th street, Charlestown, Massachusetts 02129, United States; Harvard Medical School, Department of Radiology, 149 13th street, Charlestown, Massachusetts 02129, United States.
authors.forename: Wim
authors.initials: W
authors.lastname: Vanduffel
keywords: cell-specific expression; gene transfer; histology; monkey; optogenetics; promoters
references.citation: Nat Neurosci. 2011 Mar;14(3):387-97
references.pmid: 21278729
references.citation: Front Syst Neurosci. 2011 Apr 13;5:18
references.pmid: 21811444
references.citation: J Neurosci. 2013 Sep 18;33(38):15195-206
references.pmid: 24048849
references.citation: Nature. 2010 Jul 29;466(7306):622-6
references.pmid: 20613723
references.citation: Neuron. 2009 Apr 30;62(2):191-8
references.pmid: 19409264
references.citation: Cell Biol Toxicol. 2010 Feb;26(1):1-20
references.pmid: 19830583
references.citation: Lancet. 2014 Mar 29;383(9923):1138-46
references.pmid: 24412048
references.citation: Exp Physiol. 2005 Jan;90(1):53-9
references.pmid: 15542619
references.citation: J Neurosurg. 2011 Mar;114(3):672-80
references.pmid: 20950087
references.citation: Neuron. 2001 Nov 20;32(4):565-77
references.pmid: 11719199
references.citation: Gene Ther. 2007 Jun;14(11):872-82
references.pmid: 17361216
references.citation: Hum Gene Ther Methods. 2013 Aug;24(4):205-13
references.pmid: 23808551
references.citation: Exp Neurol. 2002 Jul;176(1):66-74
references.pmid: 12093083
references.citation: Hum Gene Ther. 2011 Jun;22(6):669-77
references.pmid: 21319997
references.citation: Science. 2013 Apr 5;340(6128):1232627
references.pmid: 23559255
references.citation: Neurosci Res. 2015 Apr;93:144-57
references.pmid: 25240284
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18206-11
references.pmid: 15608064
references.citation: PLoS One. 2013 Sep 27;8(9):e76310
references.pmid: 24086725
references.citation: F1000 Biol Rep. 2011;3:11
references.pmid: 21876722
references.citation: Sci Am. 2010 Nov;303(5):48-55
references.pmid: 21033283
references.citation: Hum Mol Genet. 2010 Jan 1;19(1):147-58
references.pmid: 19837699
references.citation: Prog Neurobiol. 1998 Jul;55(4):399-432
references.pmid: 9654386
references.citation: BMC Neurosci. 2011 Jan 13;12:6
references.pmid: 21232115
references.citation: J Neurosci Res. 1999 Feb 15;55(4):504-13
references.pmid: 10723060
references.citation: Gene Ther. 2013 Dec;20(12):1178-83
references.pmid: 24067867
references.citation: Neuropsychopharmacology. 2012 Jan;37(1):296-7
references.pmid: 22157861
references.citation: Nat Genet. 1994 Oct;8(2):148-54
references.pmid: 7842013
references.citation: Neuron. 2011 Dec 8;72(5):721-33
references.pmid: 22153370
references.citation: Front Neural Circuits. 2013 Oct 11;7:162
references.pmid: 24130520
references.citation: Gene Ther. 2011 May;18(5):517-27
references.pmid: 21326331
references.citation: Mol Ther. 2010 Mar;18(3):588-93
references.pmid: 20010918
references.citation: J Comp Neurol. 1975 Jun 15;161(4):569-94
references.pmid: 1133232
references.citation: Nat Protoc. 2010 Mar;5(3):561-73
references.pmid: 20203671
references.citation: Sci Transl Med. 2009 Oct 14;1(2):2ra4
references.pmid: 20368163
references.citation: J Virol. 2002 Jan;76(2):791-801
references.pmid: 11752169
references.citation: Mol Ther. 2009 Mar;17(3):524-37
references.pmid: 19142181
references.citation: Curr Gene Ther. 2005 Jun;5(3):333-8
references.pmid: 15975010
references.citation: Mol Ther. 2010 Mar;18(3):579-87
references.pmid: 19773746
references.citation: Neurobiol Dis. 2012 Nov;48(2):179-88
references.pmid: 22001604
references.citation: Mol Ther. 2006 Oct;14(4):564-70
references.pmid: 16829205
references.citation: Neuron. 2011 Jul 14;71(1):9-34
references.pmid: 21745635
references.citation: Brain Res. 1996 Mar 25;713(1-2):99-107
references.pmid: 8724980
references.citation: Gene Ther. 2013 Mar;20(3):348-52
references.pmid: 22418061
references.citation: Mol Ther. 2011 Feb;19(2):274-83
references.pmid: 21102563
references.citation: Neuroreport. 2000 Aug 21;11(12):2669-73
references.pmid: 10976941
references.citation: Nature. 2009 Jun 4;459(7247):698-702
references.pmid: 19396159
references.citation: Hum Gene Ther. 2013 Jun;24(6):613-29
references.pmid: 23600720
references.citation: Trends Genet. 2013 Jul;29(7):403-11
references.pmid: 23623742
references.citation: Hum Gene Ther. 2007 Mar;18(3):195-206
references.pmid: 17343566
references.citation: J Comp Neurol. 2015 Oct 1;523(14):2019-42
references.pmid: 26012540
references.citation: Annu Rev Genet. 2004;38:819-45
references.pmid: 15568995
references.citation: J Neurosci. 1998 Mar 15;18(6):2129-46
references.pmid: 9482799
references.citation: J Gene Med. 2005 May;7(5):530-9
references.pmid: 15651039
references.citation: Mol Ther. 2004 Aug;10(2):302-17
references.pmid: 15294177
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12692-7
references.pmid: 20615999
references.citation: J Neural Eng. 2007 Sep;4(3):S143-56
references.pmid: 17873414
references.citation: Hum Gene Ther. 2009 Aug;20(8):845-60
references.pmid: 19419274
references.citation: J Neurophysiol. 1996 Sep;76(3):1367-95
references.pmid: 8890259
references.citation: Science. 2000 Oct 27;290(5492):767-73
references.pmid: 11052933
references.citation: J Neurosci. 1991 Jan;11(1):31-47
references.pmid: 1846011
references.citation: Curr Gene Ther. 2005 Jun;5(3):299-310
references.pmid: 15975007
references.citation: Mol Ther. 2006 Mar;13(3):463-83
references.pmid: 16412695
references.citation: Neuroscience. 2009 Jun 30;161(2):441-50
references.pmid: 19318117
references.citation: J Virol. 2004 Jul;78(13):6808-17
references.pmid: 15194756
references.citation: Invest Ophthalmol Vis Sci. 2011 Apr 25;52(5):2775-83
references.pmid: 21310920
references.citation: Mol Ther. 2012 Apr;20(4):699-708
references.pmid: 22273577
references.citation: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7332-6
references.pmid: 8692993
references.citation: Nat Neurosci. 2012 Oct;15(10):1368-70
references.pmid: 22941109
references.citation: Nature. 2012 Jul 12;487(7406):235-8
references.pmid: 22722837
references.citation: Nature. 2010 Jun 10;465(7299):788-92
references.pmid: 20473285
references.citation: Pharmacol Rev. 2011 Jun;63(2):291-315
references.pmid: 21415127
references.citation: Curr Gene Ther. 2008 Dec;8(6):461-73
references.pmid: 19075629
references.citation: J Gene Med. 2008 Jan;10(1):21-32
references.pmid: 18022932
references.citation: Nature. 2011 Mar 17;471(7338):358-62
references.pmid: 21389985
references.citation: Front Neural Circuits. 2009 Nov 09;3:19
references.pmid: 19949461
references.citation: Gene Ther. 2004 Jan;11(1):52-60
references.pmid: 14681697
references.citation: Handb Exp Pharmacol. 2007;(178):177-202
references.pmid: 17203656
references.citation: Nature. 2010 Nov 11;468(7321):277-82
references.pmid: 21068837
references.citation: J Comp Neurol. 1990 Aug 1;298(1):1-22
references.pmid: 2170466