Adeno-Associated Virus Vectors: Design and Delivery

420 Pages·2019·9.382 MB·English

by  Michael J. Castle

Methods in
Molecular Biology 1950
Michael J. Castle Editor
Adeno-
Associated
Virus Vectors
Design and Delivery
M M B
ETHODS IN OLECULAR IO LO GY
SeriesEditor
JohnM.Walker
School of Lifeand MedicalSciences
University ofHertfordshire
Hatfield, Hertfordshire,AL109AB,UK
Forfurther volumes:
http://www.springer.com/series/7651
Adeno-Associated Virus
Vectors
Design and Delivery
Edited by
Michael J. Castle
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
Editor
MichaelJ.Castle
DepartmentofNeurosciences
UniversityofCalifornia,SanDiego
LaJolla,CA,USA
ISSN1064-3745 ISSN1940-6029 (electronic)
MethodsinMolecularBiology
ISBN978-1-4939-9138-9 ISBN978-1-4939-9139-6 (eBook)
https://doi.org/10.1007/978-1-4939-9139-6
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Preface
Adeno-associated virus (AAV) vectors are essential tools for experimental gene transfer to
livinganimalsandfortheclinicaldeliveryofgenetherapies.TheFDArecentlyapprovedthe
firstAAV-basedgenetherapy,Luxturna,fortreatmentofinheritedretinaldisease,andmany
ongoing clinical trials show great promise. The widespread use of AAV vectors in the
laboratory and clinic over the past two decades has thoroughly confirmed their safety and
efficacy.TheusageofAAVvectorswillcontinuetoexpandasnewAAVtechnologiesemerge
andmoreAAV-basedtherapiesareapprovedfor thetreatmentofhumandisease.
ThisvolumeprovidesacompleteandtimelyguidetotheuseofAAVvectorsforgenetic
manipulation of mammalian tissues. The opening chapters describe the design of AAV
vectors for RNAi, for large gene delivery, and for CRISPR-mediated genome editing, as
well as droplet digital PCR titration and single-strand sequencing of AAV preparations,
ligand coupling to AAV capsids, and in situ detection of AAV mRNA expression. These
methods for the design and characterization of AAV vectors are followed by protocols for
AAVdeliverytovariouscomponentsofthecentralnervoussystem,toanumberofsensory
systems,andtoabroadrangeofothertissues.Noveltechniquessuchasultrasound-targeted
deliverytothebrain,subpialdeliverytothespinalcord,andsubILMdeliverytotheretina
areaccompaniedbychaptersthatprovideanoverviewandcomparisonofcurrentmethods
forAAVdeliverytotissuessuchasbrain,heart,liver,andlung.
Inaddition,severaldifferentprotocolsfor theproductionofAAVvectorsareprovided
throughoutthisvolume,includingiodixanolgradientpurification(Chapters3,19,and23),
CsClgradientpurification(Chapter7),asimplifiedapproachthatdoesnotrequiregradient
ultracentrifugation (Chapter 22), and heparin column purification of heparin-binding ser-
otypessuchasAAV2,AAV6,andAAV-DJ(Chapter21).
Collectively,theprotocolsinthisvolumeallowthereadertoproduce,characterize,and
deliver AAV vectors to any tissue of interest using both well-established and innovative
methods. These vital techniques will enhance the utility of AAV vectors for targeted gene
transfer to living animals and support the ongoing development of novel AAV-based gene
therapiesforhumandisease.
LaJolla,CA,USA MichaelJ.Castle
v
Contents
Preface ..................................................................... v
Contributors................................................................. ix
PART I AAV VECTOR DESIGN
1 DesignofAAVVectorsforDeliveryofRNAi............................... 3
FlorieBorelandChristianMueller
2 DesignofAAVVectorsforDeliveryofLargeorMultipleTransgenes.......... 19
AmanPatel,JunlingZhao,DongshengDuan,andYiLai
3 LigandCouplingtotheAAVCapsidforCell-SpecificGeneTransfer .......... 35
JohannaReul,AlexanderMuik,andChristianJ.Buchholz
4 QuantitativeandDigitalDroplet-BasedAAVGenomeTitration.............. 51
JulioSanmiguel,GuangpingGao,andLukH.Vandenberghe
5 Single-StrandedDNAVirusSequencing(SSV-Seq)forCharacterization
ofResidualDNAandAAVVectorGenomes ............................... 85
EmilieLecomte,AdrienLeger,MagaliePenaud-Budloo,
andEduardAyuso
6 InSituHybridizationforDetectionofAAV-MediatedGeneExpression....... 107
JacquelineE.Hunter,BrittneyL.Gurda,SeaYoungYoon,
MichaelJ.Castle,andJohnH.Wolfe
7 UseofAAVVectorsforCRISPR-MediatedInVivoGenomeEditing
intheRetina ........................................................... 123
WenhanYuandZhijianWu
PART II AAV DELIVERY TO THE CENTRAL NERVOUS SYSTEM
8 IntravenousInfusionofAAVforWidespreadGeneDelivery
totheNervousSystem................................................... 143
DominicJ.Gessler,PhillipW.L.Tai,JiaLi,andGuangpingGao
9 IntraspinalandIntracorticalDeliveryofAAVVectorsforIntersectional
CircuitTracinginNon-transgenicSpecies ................................. 165
JamesM.Conner,GregL.Bain,andJenniferN.Dulin
10 MRI-GuidedFocusedUltrasoundforTargetedDeliveryofrAAV
totheBrain............................................................ 177
ZeinabNoroozian,KristianaXhima,YuexiHuang,
BrianK.Kaspar,SebastianKu¨gler,KullervoHynynen,
andIsabelleAubert
11 AAV-MediatedGeneDeliverytotheSpinalCordbyIntrathecalInjection ..... 199
CristinaD.Peterson,AlexanderG.J.Skorput,KelleyF.Kitto,
GeorgeL.Wilcox,LucyVulchanova,andCarolynA.Fairbanks
vii
viii Contents
12 SubpialAAVDeliveryforSpinalParenchymalGeneRegulation
inAdultMammals ...................................................... 209
MarianaBravo-Herna´ndez,TakahiroTadokoro,andMartinMarsala
PART III AAV DELIVERY TO SENSORY SYSTEMS
13 PeripheralAAVInjectionforRetrogradeTransductionofDorsal
RootandTrigeminalGanglia............................................. 237
DavidC.Bloom,ZacharyL.Watson,andDonnaM.Neumann
14 SubILMInjectionofAAVforGeneDeliverytotheRetina .................. 249
PaulD.Gamlin,JohnJ.Alexander,SanfordL.Boye,
C.DouglasWitherspoon,andShannonE.Boye
15 IntracameralDeliveryofAAVtoCornealEndothelium
forExpressionofSecretoryProteins....................................... 263
Jeffrey O’Callaghan,MatthewCampbell,andPeterHumphries
16 AAV-MediatedGeneDeliverytotheInnerEar............................. 271
OmarAkilandLawrenceLustig
17 IntranasalDeliveryofAdenoviralandAAVVectorsforTransduction
oftheMammalianPeripheralOlfactorySystem............................. 283
CedricR.UytingcoandJeffreyR.Martens
18 AAV-MediatedGeneDeliverytoTasteCellsoftheTongue.................. 299
AkiyukiTarunoandMakikoKashio
PART IV AAV DELIVERY TO OTHER TISSUES
19 AAVVectorsforEfficientGeneDeliverytoRodentHearts .................. 311
EstrellaLopez-Gordo,ErikKohlbrenner,MichaelG.Katz,
andThomasWeber
20 AAV-MediatedGeneDeliverytotheLiver:OverviewofCurrent
TechnologiesandMethods .............................................. 333
BrettPalaschak,RolandW.Herzog,andDavidM.Markusic
21 AAV-MediatedGeneDeliverytotheLung................................. 361
LauraP.vanLieshout,JakobM.Domm,andSarahK.Wootton
22 SimplifiedPurificationofAAVandDeliverytothePancreas
byIntraductalAdministration ............................................ 373
PingGuo,JohnWiersch,XiangweiXiao,andGeorgeGittes
23 rAAV-MediatedGeneDeliverytoAdiposeTissue........................... 389
WeiHuang,NicholasJ.Queen,andLeiCao
24 AAV-MediatedGeneDeliverytotheEntericNervousSystem
byIntracolonicInjection................................................. 407
ReshmaGore,MaureenS.Riedl,KelleyF.Kitto,CarolynA.Fairbanks,
andLucyVulchanova
Index ...................................................................... 417
Contributors
OMARAKIL (cid:1) DepartmentofOtolaryngology-HeadandNeckSurgery,Universityof
CaliforniaSanFrancisco,SanFrancisco,CA,USA
JOHNJ.ALEXANDER (cid:1) DepartmentofHumanGenetics,EmoryUniversity,Atlanta,GA,
USA
ISABELLEAUBERT (cid:1) BrainSciences,BiologicalSciences,SunnybrookResearchInstitute,
Toronto,ON,Canada;DepartmentofLaboratoryMedicineandPathobiology,University
ofToronto,Toronto,ON,Canada
EDUARDAYUSO (cid:1) INSERMUMR1089,UniversityofNantes,CentreHospitalier
UniversitairedeNantes,Nantes,France
GREGL.BAIN (cid:1) DepartmentofBiology,TexasA&MUniversity,CollegeStation,TX,USA
DAVIDC.BLOOM (cid:1) DepartmentofMolecularGeneticsandMicrobiology,Universityof
FloridaCollegeofMedicine,Gainesville,FL,USA
FLORIEBOREL (cid:1) HoraeGeneTherapyCenter,UniversityofMassachusettsMedicalSchool,
Worcester,MA,USA
SANFORD L.BOYE (cid:1) DepartmentofPediatricsandthePowellGeneTherapyCenter,
UniversityofFloridaCollegeofMedicine,Gainesville,FL,USA
SHANNONE.BOYE (cid:1) DepartmentofOphthalmology,UniversityofFloridaCollegeof
Medicine,Gainesville,FL,USA
MARIANA BRAVO-HERNA´NDEZ (cid:1) NeuroregenerationLaboratory,Departmentof
Anesthesiology,UniversityofCalifornia,SanDiego,LaJolla,CA,USA
CHRISTIANJ.BUCHHOLZ (cid:1) Paul-Ehrlich-Institut,MolecularBiotechnologyandGeneTherapy,
Langen,Germany
MATTHEWCAMPBELL (cid:1) NeurovascularGeneticsLaboratory,SmurfitInstituteofGenetics,
UniversityofDublin,TrinityCollege,Dublin,Ireland
LEICAO (cid:1) DepartmentofCancerBiologyandGenetics,TheOhioStateUniversity,
Columbus,OH,USA;TheComprehensiveCancerCenter,TheOhioStateUniversity,
Columbus,OH,USA
MICHAELJ.CASTLE (cid:1) DepartmentofNeurosciences,UniversityofCalifornia,SanDiego,La
Jolla,CA,USA
JAMESM.CONNER (cid:1) MolecularNeurobiologyLaboratory,SalkInstituteforBiologicalStudies,
LaJolla,CA,USA
JAKOBM.DOMM (cid:1) DepartmentofPathobiology,UniversityofGuelph,Guelph,ON,Canada
DONGSHENGDUAN (cid:1) DepartmentofMolecularMicrobiologyandImmunology,Schoolof
Medicine,UniversityofMissouri,Columbia,MO,USA;DepartmentofBiomedical
Sciences,CollegeofVeterinaryMedicine,UniversityofMissouri,Columbia,MO,USA;
DepartmentofNeurology,SchoolofMedicine,UniversityofMissouri,Columbia,MO,
USA;DepartmentofBioengineering,UniversityofMissouri,Columbia,MO,USA
JENNIFERN.DULIN (cid:1) DepartmentofBiology,TexasA&MUniversity,CollegeStation,TX,
USA
CAROLYNA.FAIRBANKS (cid:1) DepartmentofNeuroscience,UniversityofMinnesota,Minneapolis,
MN,USA;DepartmentofPharmacology,UniversityofMinnesota,Minneapolis,MN,
USA;DepartmentofPharmaceutics,UniversityofMinnesota,Minneapolis,MN,USA
ix
x Contributors
PAULD.GAMLIN (cid:1) DepartmentofOphthalmologyandVisualSciences,Universityof
AlabamaatBirmingham,Birmingham,AL,USA
GUANGPING GAO (cid:1) HoraeGeneTherapyCenter,UniversityofMassachusettsMedicalSchool,
Worcester,MA,USA;LiWeiboInstituteforRareDiseasesResearch,Universityof
MassachusettsMedicalSchool,Worcester,MA,USA;DepartmentofMicrobiologyand
PhysiologicalSystems,UniversityofMassachusettsMedicalSchool,Worcester,MA,USA
DOMINIC J.GESSLER (cid:1) HoraeGeneTherapyCenter,UniversityofMassachusettsMedical
School,Worcester,MA,USA;LiWeiboInstituteforRareDiseasesResearch,Universityof
MassachusettsMedicalSchool,Worcester,MA,USA;DepartmentofMicrobiologyand
PhysiologicalSystems,UniversityofMassachusettsMedicalSchool,Worcester,MA,USA
GEORGEGITTES (cid:1) UniversityofPittsburgh/Children’sHospitalofPittsburghofUPMC,
Pittsburgh,PA,USA
RESHMAGORE (cid:1) GraduatePrograminNeuroscience,UniversityofMinnesota,Minneapolis,
MN,USA
PING GUO (cid:1) UniversityofTexasHealthScienceCenteratHouston,Houston,TX,USA
BRITTNEYL.GURDA (cid:1) ResearchInstituteoftheChildren’sHospitalofPhiladelphia,
Philadelphia,PA,USA
ROLAND W.HERZOG (cid:1) DepartmentofPediatrics,UniversityofFlorida,Gainesville,FL,
USA;DepartmentofPediatrics,IndianaUniversity,Indianapolis,IN,USA
WEIHUANG (cid:1) DepartmentofCancerBiologyandGenetics,TheOhioStateUniversity,
Columbus,OH,USA;TheComprehensiveCancerCenter,TheOhioStateUniversity,
Columbus,OH,USA
YUEXIHUANG (cid:1) PhysicalSciences,SunnybrookResearchInstitute,Toronto,ON,Canada
PETERHUMPHRIES (cid:1) OcularGeneticsUnit,SmurfitInstituteofGenetics,Universityof
Dublin,TrinityCollege,Dublin,Ireland
JACQUELINEE.HUNTER (cid:1) ResearchInstituteoftheChildren’sHospitalofPhiladelphia,
Philadelphia,PA,USA
KULLERVOHYNYNEN (cid:1) PhysicalSciences,SunnybrookResearchInstitute,Toronto,ON,
Canada;DepartmentofMedicalBiophysics,UniversityofToronto,Toronto,ON,Canada
MAKIKOKASHIO (cid:1) DepartmentofPhysiology,AichiMedicalUniversity,Nagakute,Japan
BRIAN K.KASPAR (cid:1) AveXis,SanDiego,CA,USA
MICHAELG.KATZ (cid:1) CardiovascularInstitute,IcahnSchoolofMedicineatMountSinai,New
YorkCity,NY,USA
KELLEYF.KITTO (cid:1) DepartmentofNeuroscience,UniversityofMinnesota,Minneapolis,MN,
USA
ERIK KOHLBRENNER (cid:1) CardiovascularInstitute,IcahnSchoolofMedicineatMountSinai,
NewYorkCity,NY,USA
SEBASTIANKU¨GLER (cid:1) DepartmentofNeurology,UniversityMedicalCenterGo¨ttingen,
Go¨ttingen,Germany
YILAI (cid:1) DepartmentofMolecularMicrobiologyandImmunology,SchoolofMedicine,
UniversityofMissouri,Columbia,MO,USA
EMILIELECOMTE (cid:1) INSERMUMR1089,UniversityofNantes,CentreHospitalier
UniversitairedeNantes,Nantes,France
ADRIENLEGER (cid:1) INSERMUMR1089,UniversityofNantes,CentreHospitalier
UniversitairedeNantes,Nantes,France;EuropeanMolecularBiologyLaboratory-
EuropeanBioinformatics Institute(EMBL-EBI),Cambridge,UK
JIALI (cid:1) HoraeGeneTherapyCenter,UniversityofMassachusettsMedicalSchool,Worcester,
MA,USA;LiWeiboInstituteforRareDiseasesResearch,UniversityofMassachusetts
Contributors xi
MedicalSchool,Worcester,MA,USA;DepartmentofMicrobiologyandPhysiological
Systems,UniversityofMassachusettsMedicalSchool,Worcester,MA,USA
ESTRELLALOPEZ-GORDO (cid:1) CardiovascularInstitute,IcahnSchoolofMedicineatMount
Sinai,NewYorkCity,NY,USA
LAWRENCELUSTIG (cid:1) Otolaryngology-HeadandNeckSurgery,ColumbiaUniversityMedical
Center,NewYork,NY,USA
DAVIDM.MARKUSIC (cid:1) DepartmentofPediatrics,IndianaUniversity,Indianapolis,IN,
USA
MARTINMARSALA (cid:1) NeuroregenerationLaboratory,DepartmentofAnesthesiology,University
ofCalifornia,SanDiego,LaJolla,CA,USA
JEFFREYR.MARTENS (cid:1) DepartmentofPharmacologyandTherapeutics,UniversityofFlorida,
Gainesville,FL,USA;Center forSmellandTaste,UniversityofFloridaCollegeof
Medicine,Gainesville,FL,USA
CHRISTIAN MUELLER (cid:1) HoraeGeneTherapyCenter,UniversityofMassachusettsMedical
School,Worcester,MA,USA;DepartmentofPediatrics,UniversityofMassachusetts
MedicalSchool,Worcester,MA,USA
ALEXANDERMUIK (cid:1) Paul-Ehrlich-Institut,MolecularBiotechnologyandGeneTherapy,
Langen,Germany
DONNAM.NEUMANN (cid:1) DepartmentofPharmacologyandExperimentalTherapeutics,
LouisianaStateUniversityHealthSciencesCenter,NewOrleans,LA,USA
ZEINABNOROOZIAN (cid:1) BrainSciences,BiologicalSciences,SunnybrookResearchInstitute,
Toronto,ON,Canada;DepartmentofLaboratoryMedicineandPathobiology,University
ofToronto,Toronto,ON,Canada
JEFFREYO’CALLAGHAN (cid:1) OcularGeneticsUnit,SmurfitInstituteofGenetics,Universityof
Dublin,TrinityCollege,Dublin,Ireland
BRETTPALASCHAK (cid:1) DepartmentofPediatrics,UniversityofFlorida,Gainesville,FL,USA
AMANPATEL (cid:1) DepartmentofMolecularMicrobiologyandImmunology,SchoolofMedicine,
UniversityofMissouri,Columbia,MO,USA
MAGALIEPENAUD-BUDLOO (cid:1) INSERMUMR1089,UniversityofNantes,CentreHospitalier
UniversitairedeNantes,Nantes,France
CRISTINAD.PETERSON (cid:1) DepartmentofNeuroscience,UniversityofMinnesota,Minneapolis,
MN,USA
NICHOLASJ.QUEEN (cid:1) DepartmentofCancerBiologyandGenetics,TheOhioState
University,Columbus,OH,USA;TheComprehensiveCancerCenter,TheOhioState
University,Columbus,OH,USA
JOHANNAREUL (cid:1) Paul-Ehrlich-Institut,MolecularBiotechnologyandGeneTherapy,Langen,
Germany
MAUREEN S.RIEDL (cid:1) DepartmentofNeuroscience,UniversityofMinnesota,Minneapolis,
MN,USA
JULIO SANMIGUEL (cid:1) GrousbeckGeneTherapyCenter,SchepensEyeResearchInstituteand
MassachusettsEyeandEarInfirmary,Boston,MA,USA;HarvardStemCellInstitute,
HarvardUniversity,Cambridge,MA,USA
ALEXANDERG.J.SKORPUT (cid:1) DepartmentofNeuroscience,UniversityofMinnesota,
Minneapolis,MN,USA
TAKAHIROTADOKORO (cid:1) NeuroregenerationLaboratory,DepartmentofAnesthesiology,
UniversityofCalifornia,SanDiego,LaJolla,CA,USA
PHILLIPW.L.TAI (cid:1) HoraeGeneTherapyCenter,UniversityofMassachusettsMedicalSchool,
Worcester,MA,USA;LiWeiboInstituteforRareDiseasesResearch,Universityof