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Abstract

Recombinant viruses allow for targeted transgene expression in specific cell populations throughout the nervous system. The adeno-associated virus (AAV) is among the most commonly used viruses for neuroscience research. Recombinant AAVs (rAAVs) are highly versatile and can package most cargo composed of desired genes within the capsid's ∼5-kb carrying capacity. Numerous regulatory elements and intersectional strategies have been validated in rAAVs to enable cell type–specific expression. rAAVs can be delivered to specific neuronal populations or globally throughout the animal. The AAV capsids have natural cell type or tissue tropism and trafficking that can be modified for increased specificity. Here, we describe recently engineered AAV capsids and associated cargo that have extended the utility of AAVs in targeting molecularly defined neurons throughout the nervous system, which will further facilitate neuronal circuit interrogation and discovery.

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2018-07-08
2024-03-29
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Literature Cited

  1. Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS et al. 2001. Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet. 28:92–95
    [Google Scholar]
  2. Adachi K, Enoki T, Kawano Y, Veraz M, Nakai H 2014. Drawing a high-resolution functional map of adeno-associated virus capsid by massively parallel sequencing. Nat. Commun. 5:3075
    [Google Scholar]
  3. Agha-Mohammadi S, O'Malley M, Etemad A, Wang Z, Xiao X, Lotze MT 2004. Second-generation tetracycline-regulatable promoter: Repositioned tet operator elements optimize transactivator synergy while shorter minimal promoter offers tight basal leakiness. J. Gene Med. 6:817–28
    [Google Scholar]
  4. Alisky JM, Hughes SM, Sauter SL, Jolly D, Dubensky TW Jr. et al. 2000. Transduction of murine cerebellar neurons with recombinant FIV and AAV5 vectors. Neuroreport 11:2669–73
    [Google Scholar]
  5. Allen WE, Kauvar IV, Chen MZ, Richman EB, Yang SJ et al. 2017. Global representations of goal-directed behavior in distinct cell types of mouse neocortex. Neuron 94:891–907.e6
    [Google Scholar]
  6. Beier KT, Saunders A, Oldenburg IA, Miyamichi K, Akhtar N et al. 2011. Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors. PNAS 108:15414–19
    [Google Scholar]
  7. Bello A, Tran K, Chand A, Doria M, Allocca M et al. 2009. Isolation and evaluation of novel adeno-associated virus sequences from porcine tissues. Gene Ther 16:1320–28
    [Google Scholar]
  8. Bey K, Ciron C, Dubreil L, Deniaud J, Ledevin M et al. 2017. Efficient CNS targeting in adult mice by intrathecal infusion of single-stranded AAV9-GFP for gene therapy of neurological disorders. Gene Ther 24:325–32
    [Google Scholar]
  9. Birey F, Andersen J, Makinson C, Islam S, Wei W et al. 2017. Assembly of functionally-integrated forebrain spheroids from human pluripotent stem cells to study development and disease. Nature 545:54–59
    [Google Scholar]
  10. Brown BD, Naldini L 2009. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat. Rev. Genet. 10:578–85
    [Google Scholar]
  11. Burger C, Gorbatyuk OS, Velardo MJ, Peden CS, Williams P et al. 2004. Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol. Ther. 10:302–17
    [Google Scholar]
  12. Cai D, Cohen KB, Luo T, Lichtman JW, Sanes JR 2013. Improved tools for the Brainbow toolbox. Nat. Methods 10:540–47
    [Google Scholar]
  13. Callaway EM, Luo L 2015. Monosynaptic circuit tracing with glycoprotein-deleted rabies viruses. J. Neurosci. 35:8979–85
    [Google Scholar]
  14. Castle MJ, Gershenson ZT, Giles AR, Holzbaur EL, Wolfe JH 2014a. Adeno-associated virus serotypes 1, 8, and 9 share conserved mechanisms for anterograde and retrograde axonal transport. Hum. Gene Ther. 25:705–20
    [Google Scholar]
  15. Castle MJ, Perlson E, Holzbaur EL, Wolfe JH 2014b. Long-distance axonal transport of AAV9 is driven by dynein and kinesin-2 and is trafficked in a highly motile Rab7-positive compartment. Mol. Ther. 22:554–66
    [Google Scholar]
  16. Cearley CN, Vandenberghe LH, Parente MK, Carnish ER, Wilson JM, Wolfe JH 2008. Expanded repertoire of AAV vector serotypes mediate unique patterns of transduction in mouse brain. Mol. Ther. 16:1710–18
    [Google Scholar]
  17. Cearley CN, Wolfe JH 2006. Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain. Mol. Ther. 13:528–37
    [Google Scholar]
  18. Cearley CN, Wolfe JH 2007. A single injection of an adeno-associated virus vector into nuclei with divergent connections results in widespread vector distribution in the brain and global correction of a neurogenetic disease. J. Neurosci. 27:9928–40
    [Google Scholar]
  19. Chakrabarty P, Rosario A, Cruz P, Siemienski Z, Ceballos-Diaz C et al. 2013. Capsid serotype and timing of injection determines AAV transduction in the neonatal mice brain. PLOS ONE 8:e67680
    [Google Scholar]
  20. Chan KY, Jang MJ, Yoo BB, Greenbaum A, Ravi N et al. 2017. Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nat. Neurosci. 20:1172–79
    [Google Scholar]
  21. Chang RB, Strochlic DE, Williams EK, Umans BD, Liberles SD 2015. Vagal sensory neuron subtypes that differentially control breathing. Cell 161:622–33
    [Google Scholar]
  22. Chen TW, Wardill TJ, Sun Y, Pulver SR, Renninger SL et al. 2013. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499:295–300
    [Google Scholar]
  23. Chenuaud P, Larcher T, Rabinowitz JE, Provost N, Joussemet B et al. 2004. Optimal design of a single recombinant adeno-associated virus derived from serotypes 1 and 2 to achieve more tightly regulated transgene expression from nonhuman primate muscle. Mol. Ther. 9:410–18
    [Google Scholar]
  24. Cho C, Wolfe JM, Fadzen CM, Calligaris D, Hornburg K et al. 2017. Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents. Nat. Commun. 8:15623
    [Google Scholar]
  25. Choudhury SR, Harris AF, Cabral DJ, Keeler AM, Sapp E et al. 2016. Widespread central nervous system gene transfer and silencing after systemic delivery of novel AAV-AS vector. Mol. Ther. 24:726–35
    [Google Scholar]
  26. Ciabatti E, Gonzalez-Rueda A, Mariotti L, Morgese F, Tripodi M 2017. Life-long genetic and functional access to neural circuits using self-inactivating rabies virus. Cell 170:382–92.e14
    [Google Scholar]
  27. Dana H, Mohar B, Sun Y, Narayan S, Gordus A et al. 2016. Sensitive red protein calcium indicators for imaging neural activity. eLife 5:e12727
    [Google Scholar]
  28. Danielson NB, Turi GF, Ladow M, Chavlis S, Petrantonakis PC et al. 2017. In vivo imaging of dentate gyrus mossy cells in behaving mice. Neuron 93:552–59.e4
    [Google Scholar]
  29. Davidson BL, Stein CS, Heth JA, Martins I, Kotin RM et al. 2000. Recombinant adeno-associated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system. PNAS 97:3428–32
    [Google Scholar]
  30. de Leeuw CN, Dyka FM, Boye SL, Laprise S, Zhou M et al. 2014. Targeted CNS delivery using human minipromoters and demonstrated compatibility with adeno-associated viral vectors. Mol. Ther. Methods Clin. Dev. 1:5
    [Google Scholar]
  31. de Leeuw CN Korecki AJ, Berry GE, Hickmott JW, Lam SL et al. 2016. rAAV-compatible MiniPromoters for restricted expression in the brain and eye. Mol. Brain 9:52
    [Google Scholar]
  32. Deverman BE, Pravdo PL, Simpson BP, Kumar SR, Chan KY et al. 2016. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain. Nat. Biotechnol. 34:204–9
    [Google Scholar]
  33. Dimidschstein J, Chen Q, Tremblay R, Rogers SL, Saldi GA et al. 2016. A viral strategy for targeting and manipulating interneurons across vertebrate species. Nat. Neurosci. 19:1743–49
    [Google Scholar]
  34. Drouin LM, Lins B, Janssen M, Bennett A, Chipman P et al. 2016. Cryo-electron microscopy reconstruction and stability studies of the wild type and the R432A variant of adeno-associated virus type 2 reveal that capsid structural stability is a major factor in genome packaging. J. Virol. 90:8542–51
    [Google Scholar]
  35. Duque S, Joussemet B, Riviere C, Marais T, Dubreil L et al. 2009. Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol. Ther. 17:1187–96
    [Google Scholar]
  36. Economo MN, Clack NG, Lavis LD, Gerfen CR, Svoboda K et al. 2016. A platform for brain-wide imaging and reconstruction of individual neurons. eLife 5:e10566
    [Google Scholar]
  37. Farkas SL, Zadori Z, Benko M, Essbauer S, Harrach B, Tijssen P 2004. A parvovirus isolated from royal python (Python regius) is a member of the genus Dependovirus. J. Gene Virol 85:555–61
    [Google Scholar]
  38. Fenno LE, Mattis J, Ramakrishnan C, Deisseroth K 2017. A guide to creating and testing new INTRSECT constructs. Curr. Protoc. Neurosci. 80:4.39.1–4.39.24
    [Google Scholar]
  39. Fenno LE, Mattis J, Ramakrishnan C, Hyun M, Lee SY et al. 2014. Targeting cells with single vectors using multiple-feature Boolean logic. Nat. Methods 11:763–72
    [Google Scholar]
  40. Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK 2009. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat. Biotechnol. 27:59–65
    [Google Scholar]
  41. Francois A, Low SA, Sypek EI, Christensen AJ, Sotoudeh C et al. 2017. A brainstem-spinal cord inhibitory circuit for mechanical pain modulation by GABA and enkephalins. Neuron 93:822–39.e6
    [Google Scholar]
  42. Fu H, Muenzer J, Samulski RJ, Breese G, Sifford J et al. 2003. Self-complementary adeno-associated virus serotype 2 vector: global distribution and broad dispersion of AAV-mediated transgene expression in mouse brain. Mol. Ther. 8:911–17
    [Google Scholar]
  43. Gao G, Vandenberghe LH, Alvira MR, Lu Y, Calcedo R et al. 2004. Clades of adeno-associated viruses are widely disseminated in human tissues. J. Virol. 78:6381–88
    [Google Scholar]
  44. Gombash SE, Cowley CJ, Fitzgerald JA, Hall JC, Mueller C et al. 2014. Intravenous AAV9 efficiently transduces myenteric neurons in neonate and juvenile mice. Front. Mol. Neurosci. 7:81
    [Google Scholar]
  45. Gossen M, Freundlieb S, Bender G, Müller G, Hillen W, Bujard H 1995. Transcriptional activation by tetracyclines in mammalian cells. Science 268:1766–69
    [Google Scholar]
  46. Gow A, Friedrich VL Jr., Lazzarini RA 1992. Myelin basic protein gene contains separate enhancers for oligodendrocyte and Schwann cell expression. J. Cell Biol. 119:605–16
    [Google Scholar]
  47. Gray SJ, Blake BL, Criswell HE, Nicolson SC, Samulski RJ et al. 2010. Directed evolution of a novel adeno-associated virus (AAV) vector that crosses the seizure-compromised blood-brain barrier (BBB). Mol. Ther. 18:570–78
    [Google Scholar]
  48. Gray SJ, Foti SB, Schwartz JW, Bachaboina L, Taylor-Blake B et al. 2011a. Optimizing promoters for recombinant adeno-associated virus-mediated gene expression in the peripheral and central nervous system using self-complementary vectors. Hum. Gene Ther. 22:1143–53
    [Google Scholar]
  49. Gray SJ, Matagne V, Bachaboina L, Yadav S, Ojeda SR, Samulski RJ 2011b. Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates. Mol. Ther. 19:1058–69
    [Google Scholar]
  50. Grieger JC, Choi VW, Samulski RJ 2006. Production and characterization of adeno-associated viral vectors. Nat. Protoc. 1:1412–28
    [Google Scholar]
  51. Grimm D, Lee JS, Wang L, Desai T, Akache B et al. 2008. In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adeno-associated viruses. J. Virol. 82:5887–911
    [Google Scholar]
  52. Große S, Penaud-Budloo M, Herrmann AK, Borner K, Fakhiri J et al. 2017. Relevance of assembly-activating protein for adeno-associated virus vector production and capsid protein stability in mammalian and insect cells. J. Virol. 91:e01198–17
    [Google Scholar]
  53. Haenraets K, Foster E, Johannssen H, Kandra V, Frezel N et al. 2017. Spinal nociceptive circuit analysis with recombinant adeno-associated viruses: the impact of serotypes and promoters. J. Neurochem. 142:721–33
    [Google Scholar]
  54. Hastie E, Samulski RJ 2015. Adeno-associated virus at 50: a golden anniversary of discovery, research, and gene therapy success–a personal perspective. Hum. Gene Ther. 26:257–65
    [Google Scholar]
  55. Heidenreich M, Zhang F 2016. Applications of CRISPR-Cas systems in neuroscience. Nat. Rev. Neurosci. 17:36–44
    [Google Scholar]
  56. Hillier D, Fiscella M, Drinnenberg A, Trenholm S, Rompani SB et al. 2017. Causal evidence for retina-dependent and -independent visual motion computations in mouse cortex. Nat. Neurosci. 20:960–68
    [Google Scholar]
  57. Iyer SM, Montgomery KL, Towne C, Lee SY, Ramakrishnan C et al. 2014. Virally mediated optogenetic excitation and inhibition of pain in freely moving nontransgenic mice. Nat. Biotechnol. 32:274–78
    [Google Scholar]
  58. Junyent F, Kremer EJ 2015. CAV-2—why a canine virus is a neurobiologist's best friend. Curr. Opin. Pharmacol. 24:86–93
    [Google Scholar]
  59. Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P et al. 2007. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet 369:2097–105
    [Google Scholar]
  60. Kaplitt MG, Leone P, Samulski RJ, Xiao X, Pfaff DW et al. 1994. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat. Genet. 8:148–54
    [Google Scholar]
  61. Karali M, Manfredi A, Puppo A, Marrocco E, Gargiulo A et al. 2011. MicroRNA-restricted transgene expression in the retina. PLOS ONE 6:e22166
    [Google Scholar]
  62. Kim SY, Adhikari A, Lee SY, Marshel JH, Kim CK et al. 2013. Diverging neural pathways assemble a behavioural state from separable features in anxiety. Nature 496:219–23
    [Google Scholar]
  63. Klimczak RR, Koerber JT, Dalkara D, Flannery JG, Schaffer DV 2009. A novel adeno-associated viral variant for efficient and selective intravitreal transduction of rat Müller cells. PLOS ONE 4:e7467
    [Google Scholar]
  64. Koerber JT, Jang JH, Schaffer DV 2008. DNA shuffling of adeno-associated virus yields functionally diverse viral progeny. Mol. Ther. 16:1703–9
    [Google Scholar]
  65. Koerber JT, Klimczak R, Jang JH, Dalkara D, Flannery JG, Schaffer DV 2009. Molecular evolution of adeno-associated virus for enhanced glial gene delivery. Mol. Ther. 17:2088–95
    [Google Scholar]
  66. Korbelin J, Hunger A, Alawi M, Sieber T, Binder M, Trepel M 2017. Optimization of design and production strategies for novel adeno-associated viral display peptide libraries. Gene Ther 24:470–81
    [Google Scholar]
  67. Korbelin J, Sieber T, Michelfelder S, Lunding L, Spies E et al. 2016. Pulmonary targeting of adeno-associated viral vectors by next-generation sequencing-guided screening of random capsid displayed peptide libraries. Mol. Ther. 24:1050–61
    [Google Scholar]
  68. Kotterman MA, Schaffer DV 2014. Engineering adeno-associated viruses for clinical gene therapy. Nat. Rev. Genet. 15:445–51
    [Google Scholar]
  69. Kozomara A, Griffiths-Jones S 2011. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39:D152–57
    [Google Scholar]
  70. Krebs HA 1975. The August Krogh principle: “For many problems there is an animal on which it can be most conveniently studied. J. Exp. Zool. 194:221–26
    [Google Scholar]
  71. Kügler S, Kilic E, Bähr M 2003. Human synapsin 1 gene promoter confers highly neuron-specific long-term transgene expression from an adenoviral vector in the adult rat brain depending on the transduced area. Gene Ther 10:337–47
    [Google Scholar]
  72. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T 2002. Identification of tissue-specific microRNAs from mouse. Curr. Biol. 12:735–39
    [Google Scholar]
  73. Lawlor PA, Bland RJ, Mouravlev A, Young D, During MJ 2009. Efficient gene delivery and selective transduction of glial cells in the mammalian brain by AAV serotypes isolated from nonhuman primates. Mol. Ther. 17:1692–702
    [Google Scholar]
  74. Leaver-Fay A, Tyka M, Lewis SM, Lange OF, Thompson J et al. 2011. ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules. Methods Enzymol 487:545–74
    [Google Scholar]
  75. Lee AT, Vogt D, Rubenstein JL, Sohal VS 2014. A class of GABAergic neurons in the prefrontal cortex sends long-range projections to the nucleus accumbens and elicits acute avoidance behavior. J. Neurosci. 34:11519–25
    [Google Scholar]
  76. Lee Y, Messing A, Su M, Brenner M 2008. GFAP promoter elements required for region-specific and astrocyte-specific expression. Glia 56:481–93
    [Google Scholar]
  77. Lerner TN, Shilyansky C, Davidson TJ, Evans KE, Beier KT et al. 2015. Intact-brain analyses reveal distinct information carried by SNc dopamine subcircuits. Cell 162:635–47
    [Google Scholar]
  78. Lin MZ, Schnitzer MJ 2016. Genetically encoded indicators of neuronal activity. Nat. Neurosci. 19:1142–53
    [Google Scholar]
  79. Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A et al. 2012. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484:381–85
    [Google Scholar]
  80. Lo L, Anderson DJ 2011. A Cre-dependent, anterograde transsynaptic viral tracer for mapping output pathways of genetically marked neurons. Neuron 72:938–50
    [Google Scholar]
  81. Lock M, Alvira M, Vandenberghe LH, Samanta A, Toelen J et al. 2010. Rapid, simple, and versatile manufacturing of recombinant adeno-associated viral vectors at scale. Hum. Gene Ther. 21:1259–71
    [Google Scholar]
  82. MacLaren RE, Groppe M, Barnard AR, Cottriall CL, Tolmachova T et al. 2014. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet 383:1129–37
    [Google Scholar]
  83. Maheshri N, Koerber JT, Kaspar BK, Schaffer DV 2006. Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nat. Biotechnol. 24:198–204
    [Google Scholar]
  84. McCarty DM, DiRosario J, Gulaid K, Muenzer J, Fu H 2009. Mannitol-facilitated CNS entry of rAAV2 vector significantly delayed the neurological disease progression in MPS IIIB mice. Gene Ther 16:1340–52
    [Google Scholar]
  85. McCown TJ, Xiao X, Li J, Breese GR, Samulski RJ 1996. Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. Brain Res 713:99–107
    [Google Scholar]
  86. McLean JR, Smith GA, Rocha EM, Hayes MA, Beagan JA et al. 2014. Widespread neuron-specific transgene expression in brain and spinal cord following synapsin promoter-driven AAV9 neonatal intracerebroventricular injection. Neurosci. Lett. 576:73–78
    [Google Scholar]
  87. Menegas W, Bergan JF, Ogawa SK, Isogai Y, Umadevi Venkataraju K et al. 2015. Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass. eLife 4:e10032
    [Google Scholar]
  88. Montgomery KL, Iyer SM, Christensen AJ, Deisseroth K, Delp SL 2016. Beyond the brain: optogenetic control in the spinal cord and peripheral nervous system. Sci. Transl. Med. 8:337rv5
    [Google Scholar]
  89. Morabito G, Giannelli SG, Ordazzo G, Bido S, Castoldi V et al. 2017. AAV-PHP.B-mediated global-scale expression in the mouse nervous system enables GBA1 gene therapy for wide protection from synucleinopathy. Mol. Ther. 25:2727–42
    [Google Scholar]
  90. Müller OJ, Kaul F, Weitzman MD, Pasqualini R, Arap W et al. 2003. Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. Nat. Biotechnol. 21:1040–46
    [Google Scholar]
  91. Mundell NA, Beier KT, Pan YA, Lapan SW, Göz Aytürk D et al. 2015. Vesicular stomatitis virus enables gene transfer and transsynaptic tracing in a wide range of organisms. J. Comp. Neurol. 523:1639–63
    [Google Scholar]
  92. Murlidharan G, Samulski RJ, Asokan A 2014. Biology of adeno-associated viral vectors in the central nervous system. Front. Mol. Neurosci. 7:76
    [Google Scholar]
  93. Nathanson JL, Jappelli R, Scheeff ED, Manning G, Obata K et al. 2009. Short promoters in viral vectors drive selective expression in mammalian inhibitory neurons, but do not restrict activity to specific inhibitory cell-types. Front. Neural Circuits 3:19
    [Google Scholar]
  94. Nonnenmacher M, Weber T 2012. Intracellular transport of recombinant adeno-associated virus vectors. Gene Ther 19:649–58
    [Google Scholar]
  95. Nussinovitch U, Gepstein L 2015. Optogenetics for in vivo cardiac pacing and resynchronization therapies. Nat. Biotechnol. 33:750–54
    [Google Scholar]
  96. Oh SW, Harris JA, Ng L, Winslow B, Cain N et al. 2014. A mesoscale connectome of the mouse brain. Nature 508:207–14
    [Google Scholar]
  97. Osakada F, Callaway EM 2013. Design and generation of recombinant rabies virus vectors. Nat. Protoc. 8:1583–601
    [Google Scholar]
  98. Pasca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD et al. 2015. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat. Methods 12:671–78
    [Google Scholar]
  99. Passini MA, Bu J, Roskelley EM, Richards AM, Sardi SP et al. 2010. CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy. J. Clin. Investig. 120:1253–64
    [Google Scholar]
  100. Passini MA, Watson DJ, Vite CH, Landsburg DJ, Feigenbaum AL, Wolfe JH 2003. Intraventricular brain injection of adeno-associated virus type 1 (AAV1) in neonatal mice results in complementary patterns of neuronal transduction to AAV2 and total long-term correction of storage lesions in the brains of β-glucuronidase-deficient mice. J. Virol. 77:7034–40
    [Google Scholar]
  101. Pignataro D, Sucunza D, Vanrell L, Lopez-Franco E, Dopeso-Reyes IG et al. 2017. Adeno-associated viral vectors serotype 8 for cell-specific delivery of therapeutic genes in the central nervous system. Front. Neuroanat. 11:2
    [Google Scholar]
  102. Platt RJ, Chen S, Zhou Y, Yim MJ, Swiech L et al. 2014. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell 159:440–55
    [Google Scholar]
  103. Portales-Casamar E, Swanson DJ, Liu L, de Leeuw CN, Banks KG et al. 2010. A regulatory toolbox of MiniPromoters to drive selective expression in the brain. PNAS 107:16589–94
    [Google Scholar]
  104. Pulicherla N, Shen S, Yadav S, Debbink K, Govindasamy L et al. 2011. Engineering liver-detargeted AAV9 vectors for cardiac and musculoskeletal gene transfer. Mol. Ther. 19:1070–78
    [Google Scholar]
  105. Quadrato G, Nguyen T, Macosko EZ, Sherwood JL, Min Yang S et al. 2017. Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545:48–53
    [Google Scholar]
  106. Reardon TR, Murray AJ, Turi GF, Wirblich C, Croce KR et al. 2016. Rabies virus CVS-N2cΔG strain enhances retrograde synaptic transfer and neuronal viability. Neuron 89:711–24
    [Google Scholar]
  107. Rompani SB, Müllner FE, Wanner A, Zhang C, Roth CN et al. 2017. Different modes of visual integration in the lateral geniculate nucleus revealed by single-cell-initiated transsynaptic tracing. Neuron 93:767–76.e6
    [Google Scholar]
  108. Rothermel M, Brunert D, Zabawa C, Díaz-Quesada M, Wachowiak M 2013. Transgene expression in target-defined neuron populations mediated by retrograde infection with adeno-associated viral vectors. J. Neurosci. 33:15195–206
    [Google Scholar]
  109. Salegio EA, Samaranch L, Kells AP, Mittermeyer G, San Sebastian W et al. 2013. Axonal transport of adeno-associated viral vectors is serotype-dependent. Gene Ther 20:348–52
    [Google Scholar]
  110. Samad OA, Tan AM, Cheng X, Foster E, Dib-Hajj SD, Waxman SG 2013. Virus-mediated shRNA knockdown of Nav1.3 in rat dorsal root ganglion attenuates nerve injury-induced neuropathic pain. Mol. Ther. 21:49–56
    [Google Scholar]
  111. Samaranch L, Salegio EA, San Sebastian W, Kells AP, Bringas JR et al. 2013. Strong cortical and spinal cord transduction after AAV7 and AAV9 delivery into the cerebrospinal fluid of nonhuman primates. Hum. Gene Ther. 24:526–32
    [Google Scholar]
  112. Samaranch L, Salegio EA, San Sebastian W, Kells AP, Foust KD et al. 2012. Adeno-associated virus serotype 9 transduction in the central nervous system of nonhuman primates. Hum. Gene Ther. 23:382–89
    [Google Scholar]
  113. Samulski RJ, Chang LS, Shenk T 1989. Helper-free stocks of recombinant adeno-associated viruses: Normal integration does not require viral gene expression. J. Virol. 63:3822–28
    [Google Scholar]
  114. Samulski RJ, Muzyczka N 2014. AAV-mediated gene therapy for research and therapeutic purposes. Annu. Rev. Virol. 1:427–51
    [Google Scholar]
  115. Schuster DJ, Dykstra JA, Riedl MS, Kitto KF, Belur LR et al. 2014. Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse. Front. Neuroanat. 8:42
    [Google Scholar]
  116. Schwarz LA, Miyamichi K, Gao XJ, Beier KT, Weissbourd B et al. 2015. Viral-genetic tracing of the input-output organization of a central noradrenaline circuit. Nature 524:88–92
    [Google Scholar]
  117. Shima Y, Sugino K, Hempel CM, Shima M, Taneja P et al. 2016. A mammalian enhancer trap resource for discovering and manipulating neuronal cell types. eLife 5:e13503
    [Google Scholar]
  118. Snyder BR, Gray SJ, Quach ET, Huang JW, Leung CH et al. 2011. Comparison of adeno-associated viral vector serotypes for spinal cord and motor neuron gene delivery. Hum. Gene Ther. 22:1129–35
    [Google Scholar]
  119. Suzuki K, Tsunekawa Y, Hernandez-Benitez R, Wu J, Zhu J et al. 2016. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature 540:144–49
    [Google Scholar]
  120. Swiech L, Heidenreich M, Banerjee A, Habib N, Li Y et al. 2015. In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. Nat. Biotechnol. 33:102–6
    [Google Scholar]
  121. Taymans JM, Vandenberghe LH, Haute CV, Thiry I, Deroose CM et al. 2007. Comparative analysis of adeno-associated viral vector serotypes 1, 2, 5, 7, and 8 in mouse brain. Hum. Gene Ther. 18:195–206
    [Google Scholar]
  122. Tervo DG, Hwang BY, Viswanathan S, Gaj T, Lavzin M et al. 2016. A designer AAV variant permits efficient retrograde access to projection neurons. Neuron 92:372–82
    [Google Scholar]
  123. Towne C, Pertin M, Beggah AT, Aebischer P, Decosterd I 2009. Recombinant adeno-associated virus serotype 6 (rAAV2/6)-mediated gene transfer to nociceptive neurons through different routes of delivery. Mol. Pain 5:52
    [Google Scholar]
  124. Treweek JB, Chan KY, Flytzanis NC, Yang B, Deverman BE et al. 2015. Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping. Nat. Protoc. 10:1860–96
    [Google Scholar]
  125. Treweek JB, Gradinaru V 2016. Extracting structural and functional features of widely distributed biological circuits with single cell resolution via tissue clearing and delivery vectors. Curr. Opin. Biotechnol. 40:193–207
    [Google Scholar]
  126. Van der Perren A, Toelen J, Carlon M, Van den Haute C, Coun F et al. 2011. Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9. Gene Ther 18:517–27
    [Google Scholar]
  127. Vance MA, Mitchell A, Samulski RJ, Hashad D 2015. AAV biology, infectivity and therapeutic use from bench to clinic. Gene Therapy - Principles and Challenges D Hashad 119–43 London: InTech
    [Google Scholar]
  128. Vogt CC, Bruegmann T, Malan D, Ottersbach A, Roell W et al. 2015. Systemic gene transfer enables optogenetic pacing of mouse hearts. Cardiovasc. Res. 106:338–43
    [Google Scholar]
  129. Wagner MJ, Kim TH, Savall J, Schnitzer MJ, Luo L 2017. Cerebellar granule cells encode the expectation of reward. Nature 544:96–100
    [Google Scholar]
  130. Wall NR, Wickersham IR, Cetin A, De La Parra M, Callaway EM 2010. Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus. PNAS 107:21848–53
    [Google Scholar]
  131. Wang S, Olumolade OO, Sun T, Samiotaki G, Konofagou EE 2015. Noninvasive, neuron-specific gene therapy can be facilitated by focused ultrasound and recombinant adeno-associated virus. Gene Ther 22:104–10
    [Google Scholar]
  132. Weitzman MD, Linden RM 2011. Adeno-associated virus biology. Methods Mol. Biol. 807:1–23
    [Google Scholar]
  133. Wertz A, Trenholm S, Yonehara K, Hillier D, Raics Z et al. 2015. Single-cell-initiated monosynaptic tracing reveals layer-specific cortical network modules. Science 349:70–74
    [Google Scholar]
  134. Williams EK, Chang RB, Strochlic DE, Umans BD, Lowell BB, Liberles SD 2016. Sensory neurons that detect stretch and nutrients in the digestive system. Cell 166:209–21
    [Google Scholar]
  135. Xiao C, Cho JR, Zhou C, Treweek JB, Chan K et al. 2016. Cholinergic mesopontine signals govern locomotion and reward through dissociable midbrain pathways. Neuron 90:333–47
    [Google Scholar]
  136. Xie J, Xie Q, Zhang H, Ameres SL, Hung JH et al. 2011. MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted transgene expression. Mol. Ther. 19:526–35
    [Google Scholar]
  137. Xie Q, Bu W, Bhatia S, Hare J, Somasundaram T et al. 2002. The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy. PNAS 99:10405–10
    [Google Scholar]
  138. Xie Q, Spear JM, Noble AJ, Sousa DR, Meyer NL et al. 2017. The 2.8 Å electron microscopy structure of adeno-associated virus-DJ bound by a heparinoid pentasaccharide. Mol. Ther. Methods Clin. Dev. 5:1–12
    [Google Scholar]
  139. Yang B, Li S, Wang H, Guo Y, Gessler DJ et al. 2014a. Global CNS transduction of adult mice by intravenously delivered rAAVrh.8 and rAAVrh.10 and nonhuman primates by rAAVrh.10. Mol. Ther. 22:1299–309
    [Google Scholar]
  140. Yang B, Treweek JB, Kulkarni RP, Deverman BE, Chen CK et al. 2014b. Single-cell phenotyping within transparent intact tissue through whole-body clearing. Cell 158:945–58
    [Google Scholar]
  141. Ye L, Allen WE, Thompson KR, Tian Q, Hsueh B et al. 2016. Wiring and molecular features of prefrontal ensembles representing distinct experiences. Cell 165:1776–88
    [Google Scholar]
  142. Yla-Herttuala S 2012. Endgame: Glybera finally recommended for approval as the first gene therapy drug in the European Union. Mol. Ther. 20:1831–32
    [Google Scholar]
  143. Zhang H, Yang B, Mu X, Ahmed SS, Su Q et al. 2011. Several rAAV vectors efficiently cross the blood-brain barrier and transduce neurons and astrocytes in the neonatal mouse central nervous system. Mol. Ther. 19:1440–48
    [Google Scholar]
  144. Zhao Z, Wang L, Gao W, Hu F, Zhang J et al. 2017. A central catecholaminergic circuit controls blood glucose levels during stress. Neuron 95:138–52.e5
    [Google Scholar]
  145. Zhong L, Li B, Mah CS, Govindasamy L, Agbandje-McKenna M et al. 2008. Next generation of adeno-associated virus 2 vectors: Point mutations in tyrosines lead to high-efficiency transduction at lower doses. PNAS 105:7827–32
    [Google Scholar]
  146. Zingg B, Chou XL, Zhang ZG, Mesik L, Liang F et al. 2017. AAV-mediated anterograde transsynaptic tagging: mapping corticocollicular input-defined neural pathways for defense behaviors. Neuron 93:33–47
    [Google Scholar]
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