controlspanel1

499A.
B.
controlAAVlacZChapter3,Figure5.
CellulartransductionwithAAVlacZ:A:NeonatalcardiomyocytesB:FetalcardiactissueC:AdultcardiomyocytesChapter15,Figure1.
HistologicalanalysisofmiceharboringAT·]cardiomyocytegrafts.
(A)Surveyphotomicrographofa3monthpost-implantationAT-]cardiomyocytegraft,HandEstained.
Magnification=]OOx.
(B)ImmunohistologicallocalizationofT-AginanAT-]graftinasectionadjacenttothatshowninpanelA.
NotetheconcordancebetweendensehematoxylinstainingandthepresenceofT-Ag.
Magnification=100x.
FromAm.
J.
Physiol.
264(HeartCirc.
Physiol.
33):Hl727-H1733,1993.
500Chapter15,Figure5.
HistologicalanalysisofmicewithC2C12myocardialgrafts.
(A)C2C12cardiacgraftharvestedat22dayspost-implantation,HandE.
Notethejuxtapositionofgraftmyotubeswithcardiomyocytes.
(B)Immunofluorescenceassayforskeletalmyosinheavychain(antibodyMY-32)witharhodamine-conjugatedsecondaryantibody.
SectionshowsthesamegraftdepictedinA;redfluorescencemarksthelocationofgraftmyotubes.
NotethatcardiacmyocytesdonotreactwithMY-32(compareAandB).
From!
.
Clin.
lnvest.
1993.
92:1548-1554.
Chapter15,Figure8.
HistologicanalysisofC2(280)intracardiacgraft.
A)HandEanalysisofC2(280)intracardiacgraft6weekspostimplantationand2weeksafterzincsulfateinduction.
Graftcanbedistinguishedfromhostmyocardiumbytheweakeosinstaining.
Magnificationx100.
B)ImmunohistologicanalysisforTGF-f31expressioninaC2(280)intracardiacgraft(sectionserialwiththatdepictedinpanelA).
BrownimmunoperoxidasereactionproductindicateshighlevelsofrecombinantTGF-f31expressionintheengraftedcells.
Magnificationx100.
From!
.
Clin.
lnvest.
1995.
95:114-121.
501Chapter15,Figure9.
ImmunohistologyforvWFlocalizationinthemyocardiumborderingaTGF-f3IexpressingC2(280)graft.
Thedottedlinedemarcatesthegraft/myocardiumborder;thegraftislocalizedintheupperleftcornerofthemicrograph.
NotethehighcapillarydensityasevidencedbyvWFimmunoreactivity.
Magnificationx400.
B)ImmunohistologyforvWFlocalizationinthemyocardiumborderingacontrolC2C12graft.
Thedottedlinedemarcatesthegraft/myocardiumborder;thegraftislocalizedintheupperleftcornerofthemicrograph.
TheabsenceofsignificantvWFimmunoreactivitysuggestsrelativelylowcapillarydensity;positivesignalcanbeseenwithinthegraftitself.
Magnificationx400.
FromJ.
Clin.
Invest.
1995.
95:114-121.
Chapter15,Figure10.
vWFimmunohistology.
C2(280)engraftedanimalsmaintainedonhighdietaryzincfor6.
5weeksweregivenabolusinjectionof3H-thymidine,andheartsectionswereprocessedsimultaneouslyforvWFimmunohistologyandautoradiography.
ThepanelshowsanepifluorescenceviewofabloodvesselinthemyocardiumadjacenttotheTGF-f31expressingC2(280)graft.
MagnificationxlOOO.
B)SamefielddepictedinpanelAabove,butviewedunderbrightfieldmicroscopy.
Notethepresenceof6syntheticvascularendothelialcells,asevidencedbythepresenceofnuclear-localizedsilvergrainsintheautoradiogram.
Arrowindicatesasyntheticcellinthemedia.
Magnificationx1,000.
FromJ.
Clin.
Invest.
1995.
95:114-121.
502Chapter16,Figure1.
{3-galactosidaseExpressioninPrimaryRabbitSkeletalMyoblastsbeforeandafterMyoblastTransfer.
A.
{3-galactosidaseExpressioninLeftVentricleTwoWeeksafterMyoblastTransfer.
Autologousmyoblastsdoublyinfectedwithadenovirusexpressingbothnuclearandcytoplasmic{3-galactosidaseundercontroloftheCMVLTRweredirectlyinjectedatthesiteofthesutureintomyocardium.
Attwoweeksafterinjection,leftventricle(LV)washarvestedandstainedfor{3-galactosid~rssion(bluecolor).
Sections2and3areapproximately14x13x2.
5mmdemanstratingtheextentof{3-galactosidasestainingthroughoutLV.
B.
NuclearandCytoplasmicf3-galactosidaseExpressioninLV.
Sectionsfromtheabovetissuewhichstainedpositivelyfor{3-galactosidasewereexaminedhistologically.
Alightmicrograph(450xmagnification;bar=50p)of{3-galactosidaseexpressioninthecytoplasmandnucleusofmyoblastswithinan8pmmethacrylatesectionsurroundingthesuturesiteisdepicted.
Theunfilledarrowindicatesamultinucleatedmyocytesimilartothatinpanel1Cexpressingcytoplasmicf3-galactosidase;thefilledarrowindicatesacellexpressingnuclearf3-galactosidasesimilartothatdepictedinpanel1D.
CandD.
InVitrof3-galactosidaseExpressioninPrimaryRabbitSkeletalMyoblasts.
PrimaryrabbitskeletalmyoblastswereinfectedatanMOlof500withadenovirusexpressingcytoplasmic(lC)ornuclear(1D)13-galactosidaseundercontroloftheCMVLTRandculturedfor62hourspriortofuationandstaining.
Theunfilledarrowindicatesamultinucleatedcellexpressingcytoplasmic{3-galactosidase.
Thefilledarrowindicatesamyoblastexpressingnuclear{3-galactosidaseonly,whereasinthemyoblastabovethearrow,f3-galactosidaseisexpressedinboththecytoplasmandnucleus,presumablyduetothehighlevelof{3-galactosidaseexpressionandsubsequentsaturationofnucleartransportmechanisms.
INDEXAAAV2genomestructureof,59--60humanresponseto,58integrationof,62--63lifecycleof,60--62virionstructureof,60wild-typevs.
recombinant,66--67AAV3,58AAV5,58AAVS1site,63Acidicfibroblastgrowthfactor,308-309Acquiredimmunodeficiencysyndrome(AIDS),68Adeno-associatedvirusvectors,57-76,221.
SeealsoAAV2;AAV3;AAV5advantagesof,57-58AIDStherapywith,68braingenetransferwith,69-70incardiovasculargenetherapy,70-74cysticfibrosisgenetherapywith,68--69epidemiologyandhostrangeof,58-59genetherapyusesof,67-74hemoglobinopathytherapywith,68hostcellcyclewith,65naturalhistoryof,58--63forParkinson"sdisease,69-70replicationof,61--62safetyandefficacyof,65targetcelldeliveryof,61targetsof,67vectorbiologyof,63--67vectorconstructionandpackagingof,63--65vectorintegrationandpersistencein,66--67vectortransductionof,67--68wild-typevs.
recombinant,66--67Adenosinedeaminasegenetransfer,259-260insmoothmusclecells,281-285Adenovirus(es)animalmodelsofinfectionwith,385inchildrenwithmyocarditis,381,383-384myocardialdiseasefrom,historicalevidenceof,379-380myocardialdiseasefrom,peRevidenceof,380-384myocardiumand,377-388replication-competent,26Adenovirus(es),human,14-21classificationof,14-15clinicalaspectsof,15-16genomeof,16-17,18lifecycleof,16-17molecularbiologyof,16-172ndand3rdgenerationsof,20-21replication-deficientvectorsof,17-211stgenerationof,17-20structureof,14Adenovirus(es),LacZexpressing,E1-1E4-,42-50constructionof,42-47efficiencyandsafetyof,47-49hightiterproductionof,49-50Adenovirus(es),recombinant,.
25-50504E1-IE4-deleted,49-502ndgenerationof,32-33Istgenerationof,26-27Adenovirusdelivery,viacatheters.
SeeDelivery,adenoviralAdenovirus-mediatedgenetransfer.
SeeGenetransfer,adenovirus-mediatedAdenovirusvectors.
SeeVectors,adenoviralAd1OOjJGal,44Ad808jJGal,44Adl004jJGal,44AdI007jJGal,44AdI014jJGal,42-44constructionof,46E4+absencein,47Ad5genome,26-27AdRSVjJGal,43,47Affinity-baseddelivery,179-182chimericantibodiesin,181-182Albuminpromoter,461Alkalinephosphatasegenetransfer,281-285Amplicon,75Angiogenesisendothelialcellproliferationvs.
migrationin,315fromexperimentalvascularobstruction,316hypoxiaand,320-321fromskeletalmyoblastgrafting,344-345Angiogenesis,therapeutic,307-325cytokine-stimulatedcellularproliferationas,315-319cytokinesynergismin,321-324directvs.
indirectcytokinesin,319-321endothelium-dependentvasomotortoneand,311-312initiationof,315introductionto,307-311forvascularinsufficiency,308,309viacytokinearterialgenetransfer,312-314Angioplasty,lowpressure,207Angiotensinconvertingenzyme(ACE)HVJ-liposomedeliverysystemand,130-132inhibitedexpressionof,127vascularexpressionof,131-132,244Angiotensinconvertingenzyme(ACE)inhibitors,453-454AngiotensinII,144inhibitionofreceptorfor,454Animalmodels,240Antibodieschimeric,181-182astargetingagents,228-229Antibody,labelingwith,229Antisenseapproaches,143-168,147-156finalcommonpathwaygenesas,146-147mechanismsof,152-153oligonucleotidecellentrywith,151-152oligonucleotidechemistryin,149-151oligonucleotidetechniquesas,147-156sequenceselectionin,147-149sequencetargetsin,153-154technologyproblemswith,154-156invivoantisensestudies,156-168Antisenseoligomers,125-127Antisensesequencesbiologicaleffectof,158targetsof,153-154Antisensestudies,invivo,156-168onc-myb,157-160controlsin,158deliveryin,effectivenessof,166deliveryin,modeof,164-166deliveryvehiclesin,qualityandconsistencyof,167extravascularadministrationin,160-161neurologicalapplicationsof,167-168oligonucleotidesynthesisqualityin,166inratcarotidinjurymodel,157sequencespecificityin,161,163-164spatialdistributionofeffectin,162Antisensetechnologyproblems,154-156controlstoprevent,156intercellularproteinbinding,155partialsequencematches,154-155RNA-oligonucleotidehybrids,155a-Antitrypsindeficiency,398-399,402,410-413Apo.
SeeApolipoproteinApolipoproteinAIadenoviral-mediatedexpressionof,438-439adenoviralvectordeliveryof,438-439ApolipoproteinBmRNAeditingprotein,441-442Apolipoproteindisorders,396-397,402ApolipoproteinEadenoviralvectordeliveryof,437-438deficiencyof,419-420functionof,437"Arteriovenousreversal,"317Arylsulfatasegene,70Asialoglycoproteinreceptor,96AT-lcellgrafting,334-338administrationof,334ECGrecordingsof,337EManalysisof,336-337graftsuccesswith,334-335immunohistologicalanalysisof,335lactatedehydrogenaselevelsin,335-336,338Atherosclerosis,localized,397-398Avlvectors,17-20Av2vectors,20Av3vectors,20-21BBalloontoarteryratio,211Basicfibroblastgrowthfactor,144,308hypoxicregulationof,321postmyocardialischemiaactionsof,368smoothmusclecellmitogeniceffectsof,324synergismwithVEGFof,321-324Beta-galactosidasegenetransfer,281-285Bloodpressurehigh.
SeeHypertension;Kallikrein-kininsystemkallikreinregulationof,455BODWY,334Braingenetherapy,69-70HSVvectorfor,74-76cCalciumphosphatecoprecipitation,94Cardiacrejection,adenoviralPCRof,381-382Cardiomyocyte,71adulttransductionof,73embryonictransductionof,72-73neonataltransductionof,71-72transductionof,71-73Cardiomyopathy,dilated,378CardiovasculargenetherapyAAV-basedvectorfor,70-74incardiomyocytes,71-73celltargetsof,70-71inendothelialcells,73perfusionmodelof,73strategiesusedin,71Catheter(s),183-187Channelledballoon,185-186designsof,early,202-206Dispatch,184,203-204,208,212doubleballoon,183,202-203efficiencyof,207-216.
SeealsoCatheterefficiencyfordetailedlistingsflowrateof,212-214hydrogel,186Infusasleeve,184-185microporous,185,203-204,208-216microporousballoon,203-204,206-216needleinfusion,187nippleballoon,186-187orificemediatedjeteffectsfrom,205porousballoon(Wolinsky),183-184,203,204-205,207stentedballoon,186505transport,185Catheterdelivery,local,179-194adenoviralvs.
lipofectintransferin,192affinity-based,179-182cathetersusedin,183-187deliveryefficiencyin,190-193ofgenes,187-194intramuralretentionin,193-194iontophoreticfacilitateddiffusionin,187safetyin,187-189vascularinjurywith,188vascularresponseto,189-190viralcontaminationfrom,189-190,191Catheterdeliveryefficiency,207-216.
SeealsoCatheterefficiencyfordetailedlistingsCatheterefficiency,207-216designof,208-209diffusionandconvectionin,209hearttissuepressurein,212hydrogeland,214inflationmethodand,215-216infusiontimeandflowratein,212-214pressureatdrugdeliveryinterfacein,214pressure-augmenteddiffusionand,214pressuregradientsin,210retainedsubstancesand,214studiesof,209Catheterfluiddynamics,201-216designsfor,early,202-206efficiencyof,207-216histopathologyand,206-207holesizeand,206inmicroporousballoon,206-216Cationicliposomes,97,103-104efficacyofuptakein,125-126C2C12myoblastgrafting,338-342.
SeealsoMyoblastgraftingfordetailedlistingsCellcyclegenes,154Cellcycleprogression,146-147Cellgrafting,AT-Icardiomyocyte,334-338.
SeeAT-lcardiomyocytefordetailedlistingsCellgrowthmodification,245-249cytostaticapproachto,245,248-249cytotoxicapproachto,245-246retinoblastomagenein,248-249thymidinekinasegenein,246-248usingadenoviralvectors,247-248293cellline,El-1E4-deletedRAdsfrom,39-42Cellproliferationdynamics,vascular,293-304labellingindicesin,299-300limitationsofmodelingof,302-303inmalignancy,fetus,restenosis,300-301mathematicalmodelof,295-297,297-298506minimallumendiameterand,297-298populationdoublingtimeand,298-301inrestenosisafterangioplasty,293-294restenosisgenetherapyand,301-302therapiestodecrease,301-302Cellproliferationmodel,295-298Cellulargrafting,333-350.
SeealsoDelivery,cell-basedmyocardial,fordetailedlistingsCentralnervoussystemgenetherapyAAVvectorfor,69-70herpessimplexvirusvectorfor,74-76Channelledcatheter,185-186Chimericantibodies,181-182Cholesterolgenetherapyfor,434proteinsinhomeostasisof,440Cholesterol7a-hydroxylaseadenoviralvectordeliveryof,440-441functionandregulationof,440Ciselementdecoys,128-129,133Cloningcapacity,increasein,48c-myb,146-147c-myc,161-163neointimaleffectsof,193Colchicine,193Collateral(s)chronicperfusionthrough,311-312formationof,307-325.
SeealsoAngiogenesis,therapeutic,fordetailedlistingsstimulatingformationof,321-323Collateralvesseldevelopmentaugmentationof,316-317cellularproliferationin,317fromendothelialcellproliferation,316VEGFeffecton,318Conductance,hydraulic,210,212Congestiveheartfailure,355-356epidemiologyof,355-356,357myoblasttransfertherapyfor,356-372.
SeealsoMyoblasttransferfordetailstherapiesfor,356,357Constitutivepromoters,6Contamination,replication-competentadenovirus,26solutionto,48duringviralstockpreparation,48-49Convection,209Convectivemasstransfer,486-488,491Coxsackievirus,378C2(280)transfectedskeletalmyoblastgrafting,342-348CysticfibrosisAAV-basedvectorgenetherapyfor,68-69adenoviralvectorsfor,445Cytokines,angiogenic,307-308arterialgenetransferof,312-314Ddirectvs.
indirect,319-321synergismof,321-324Dallascriteria,379-380DC-chol,98liposomesof,100-101DDAB,99DEAE-dextrandelivery,93-94Delivery,adenoviralviacatheter,192Delivery,cell-basedmyocardial,333-350AT-lcellgrafting,334-338C2C12myoblastgrafting,338-342C2(280)transfectedskeletalmyoblastgrafting,342-348Delivery,DNA,92-102.
SeealsoNonviralvectorsfordetailedlistingsDelivery,gene,219-232barriersto,220cell-basedvascular,255-274.
SeealsoEndothelialcellgenetransferfordetailedlistingscharacteristicsofsystemfor,220ofkallikreingene,457-458,459lysosomaldegradingproteinsand,224nonbiologictechniquesof,222-223nonviral,222-224nonviral,sustained-release,224-228parametersof,494polymergelsin,224-225polymermicrospheresin,225-226polymermicrospheresin,membrane-freedeliverywith,226-228polymernanospheresin,225-226receptor-mediated,223smoothmusclecellcarriersin,279-288.
SeealsoSmoothmusclecellgenetransferforsystemicexpression,395-425.
SeealsoGenetherapy,systemic,fordetailedlistingstargeted,228-231.
SeealsoTargeteddeliveryfordetailedlistingsviaadenoviralvector.
SeeVector,adenoviralviral,221-222,259-264viralcapsidproteinsin,223,226Delivery,local,180.
SeealsoCatheterbaseddelivery,localconvectivetransferin,486-488,491diffusivetransferin,486,488-491intodiseasedvessels,484-485efficiencyof,478-480endovascularmechanismsof,485-491intramural,491-492localpermeationin,484optimizationof,481-485peri-andextra-vascular,485pericardial,492-493perivascularapproachesto,491-493pharmacokineticsof,477-493.
SeealsoPharmacokineticsfordetailsspecificityof,481-482transvascular,491-492vs.
systemicdelivery,482-483Delivery,protein,333-350cell-basedmyocardial,333-350.
SeealsoDelivery,cell-basedmyocardial,fordetailsDeliverymethods.
SeealsospecifictypesHVJ-liposome,111-136.
SeealsoHVJ-Iiposomedeliverysystemfordetailedlistingslimitingstepsin,104typesof,103-104Dendrimers,101-102,104Deoxyribonucleicacid.
SeeDNADiabetesmellitus,398Diffusion,209iontophoreticfacilitated,187pressure-augmented,214Diffusioncoefficient,489Diffusivemasstransfer,486,488-491Dispatchcatheter,184,203-204,208,212DMRIE,100,101DNAdirectinjectionof,102lipid-mediateddeliveryof,96--101DNAbindingprotein,31DNAdelivery,92-102.
SeealsoNonviralvectorsfordetailedlistingsDNAvirusvectors,57-76.
SeealsoAdeno-associatedvirusvectorsDOGS,99DOPE,98,99,100,101DORI,100DORIE,100DOSPA,99DOTAP,98,99,101DOTMA,98,99,101Doubleballooncatheters,183,184.
SeealsoDispatchcatheterinfusiontechniquewith,202-203Double-copyvector,12Doublingtime,population,298-301Drugadministration,intramural.
SeeCatheter(s)Drugresistancegene,11EEIAactivationofE2Aepromoterby,38functionsof,30substitutingactivityof,30-31E2Ageneproductinactivationin,31-33tsmutantof,3-33Echovirus,378E4deletionmutants,35delE4/0RFX+,40genomeorganizationin,34,36H2d1808,40MLTUdeficiencyin,35-36El-1E4-adenovirus,LacZ-expressingconstructionof,42-44,44-47efficiencyandsafetyof,47-49high-titerproductionof,49-50El-IE4-adenoviruses,25-50.
SeealsoAdenovirus(es)fordetailedlistingsE2F,128E2Fdecoy,128,133Efficiency507ofcatheters,208-216.
SeealsoCatheterefficiencyfordetailedlistingsofmicroporousballooncatheter,207-216.
SeealsoCatheterefficiencyfordetailedlistingsElectroporationdelivery,94-95Endocytosis,receptor-mediated,95-96,103-104,151Endothelialcellactivation,315Endothelialcellgenetransfer,255-274biologicallyrelevantexpressionvia,272directinvivo,270-272effectof,onnormalcellfunction,274exvivo,265-269ofFactorIXgenes,262-263geneexpressionin,long-term,273-274geneexpressionin,regulated,273genestransferredwith,258GMECimplantationin,265-269.
SeealsoGeneticallymodifiedendothelialcellofhumantissueplasminogenactivator,260-262ofhumanumbilicalveinendothelialcells,260oflacZ,aI-antitrypsin,catalasegenes,263physicalmethodsfor,264ofratgrowthhormoneandadenosinedeaminasegenes,259-260retroviral,260systemidealsin,272-273transductionvia,73vectorsusedwith,257invitro,physicalmethodsfor,264invitro,virus-mediated,258-264Endothelialcellproliferationincollateraldevelopment,316--317fromdirectvs.
indirectcytokines,319-321508Endothelium,cardiovascularincancertherapy,256functionsof,256,259asgenetransfertarget,255-256regionsof,255Endothelium,vascular,70Endothelium-dependentvasomotortone,311-312VEGFimprovementof,312Endothelium-derivedrelaxingfactor,311-312Enhancers,tissue-specific,88Epidermalgrowthfactor,144Epidermalgrowthfactorreceptor,182Epitopetagging,91-92Epo.
SeeErythropoietinE4region.
SeealsoErlE4-adenovirusesgenomestructureof,33-34,36manipulationof,33-36Erythropoietindeficiency,398,42~22,425Expressionmodification,antisenseapproachesto,143-168.
SeealsoAntisenseapproachesfordetailsExvivogenetherapy,4,89,399-400celltypeefficacyin,404drawbacksof,399-400Fendothelialcelltransferas,265-269forhumangrowthhormonedeficiency,422-424,425myoblast-mediated,362-365withplasmidvector,404withretroviralvector,405systemic,399-400vs.
invivo,369,400,425FactorIX,413-414,416-419genetransferof,262-263FactorVIII,402,413-415FactorV-Leiden,397Familialhypercholesterolemia.
SeeHypercholesterolemia,familialFGF-2,243FGF-lgene,240,243Fibroblastsexvivogenetherapywith,404asretroviralvectors,405systemicgenetherapywith,399,403,425Finalcommonpathwaygenes,146-147Finiteelementmodeling,210Fluidflux,transmural,211Fluidfluxrate,486-487Folatereceptor,96Fractionalintramuraldelivery,448,478,487lowvaluesof,481-482Fractionalregionaldelivery,478-479FractionalvirionadsorptionF,480Fusionstepsin,113-115betweenvirusesandhostcells,112-115Fusogenicmembraneglycoproteins,116-117transferof,118GGels.
SeePolymergelsGenedelivery.
SeeDelivery,geneGenedelivery,localdeliveryefficiencyin,190-193intramuralretentionin,193-194safetyin,187-189vascularresponseto,189-190Geneexpressioncontrolof,spatial,89controlof,temporal,88decoyinhibitionof,133-134endogenousvs.
transfectionproductsin,91-92HVJ-liposomemodificationof,124--130inactivationof,witholigonucleotides,125-127recombinant,strategiesfor,265specificmanipulationof,130-132transientvs.
stable,90"Genegun,"222Genes.
Seealsospecificgenescell-cyclespecific,146-147Geneswitchtechnology,88Genetherapyadenoviral.
SeeAdenovirus(es);Vectors,adenoviraladenoviralvs.
lipofectin,192withangiogeniccytokines,312-314cellproliferationdynamicsand,293-304.
SeealsoCellproliferationdynamicsfordetailsdeliveryof.
SeeDelivery,genedirect,240.
SeealsoVectorsdirectinvivo,270-272.
SeealsoInvivogenetherapyexvivo.
SeeDelivery,cell-basedmyocardial;Exvivogenetherapygoalof,86historyandscopeof,3-4mechanicalaspectsof,179-194myocardiumand,386-387ofratgrowthhormoneandadenosinedeaminasegenes,259-260somatic,462,466-467withvascularsmoothmusclecells,279-288.
SeealsoSmoothmusclecellgenetransferinvitro,259-264.
SeealsoInvitrogenetherapyinvivo,26,89.
SeealsoInvivogenetherapyGenetherapy,adenovirus-mediated,26-28CMVVS.
RSVfor,inskeletalmyoblasts,363-365E2functioninactivationwith,31-32hostresponseto,29-3Imyoblastdeliveryvia,363-364neonataladministrationof,28,30pathologywith,26-27,28-33transientexpressionof,26-33Genetherapy,endothelial,255-274.
SeealsoEndothelialcellgenetransferfordetailedlistingsvectorsusedfor,257Genetherapy,myoblast-mediated,358.
SeealsoMyoblasttransfertherapyGenetherapy,systemic,395-425adenoviralvectorefficacyas,404-405fora-antitrypsindeficiency,410-413celltypevectorefficacywith,402-406forerythropoietindeficiency,420-422,425examplesof,407-424exvivo.
SeeExvivogenetherapyfactorsin,40I-402forfamilialhypercholesterolemia,407-410forgrowthhormonedeficiency,422-424,425forhemophilia,413-419forhemostasis,396-398forhyperlipoproteinemia,419-420forlipiddisorders,396-397plasmidDNAefficacywith,403-404forproteindeficiencies,398-399retroviraIvectorefficacyin,405-406forserumproteindeficiencies,410-424invivo.
SeeInvivogenetherapyGeneticallymodifiedendothelialcells,256angiogenesis-driveimplantationof,268-269catheterandprostheticgraftimplantationof,266-268implantationof,265-269Genetranscription,inhibitionof,154Genetransfersystems,II1-168.
SeealsoGenetherapy;VectorsGlucocerebrosidasegene,70GraftingAT-lcell,334-338myoblast,338-342skeletalmyoblast,342-348Growthfactorgenes,240-245Growthfactors.
Seealsospecificgrowthfactorsacidicfibroblast,308-309angiogenic,307-308angiogenicindirect,319-321astargetingagents,228Growthhormonehuman,402rat,259-260509Growthhormonedeficiency,402,422-424,425Growthmodification,cell,245-249.
SeealsoCellgrowthmodificationfordetailedlistingsGlvector,11-12HHalflife,targetprotein,153-154H5dllOI4,42-43HemagglutinatingvirusofJapan(HVJ).
SeeHVGHematopoieticcells,67-68Hemoglobinopathies,68HemophiliaFactorIXtherapyfor,413-414,416-419FactorVIIItherapyfor,413-414,415systemicgenetherapyfor,398,413-419Hemostasisdisorders,396-398Heparinintramuralretentionof,193smoothmusclecelleffectof,146-147Hepaticgenetherapyexvivovs.
invivo,399-400forfamilialhypercholesterolemia,407-410forkallikreingenedelivery,467.
SeealsospecificdisordersHepatocytesretroviralvectordeliveryto,406,409systemicgenetherapywith,399,403,425vectoraccumulationin,435Herpessimplexvirus(vector)advantagesof,74forCNSgenetherapy,74-76difficultiesof,75recombinantHSVconstructionwith,75-76HighdensitylipoproteinapoAIeffecton,438functionof,438Highdensitylipoproteinreceptor.
SeeHypercholesterolemia,familialHighmobilitygroup1,124,126-127HMG-CoAreductase,440Host-vectorinteractions,21510Humangrowthhormonedeficiency,402,422-424,425Humanumbilicalveinendothelialcells,260HVJcharacterizationof,113fusionpropertiesof,113-114isolationof,112-113productionandstorageof,119HVJ-liposomedeliverysystem,111-136advantagesof,135antisenseoligomersin,125-126bindingin,118decoystrategyin,129,133efficacyofuptakein,125-126,134,135asexperimentaltool,133futurestudieson,135-136geneexpressionmodificationwith,124-130HVJproductionandstoragein,119HVJviralenvelope-mediatedtransfectionin,115-117ininactivationofgeneexpression,125-129increasedefficiencywith,193liposomecomposition/purityin,122liposomeencapsulationin,121-122liposomeproductionin,120-121methodologicalconsiderationswith,118-124negativelychargedphospholipidsin,122-123pHrangeofmembranefusionin,116qualityassurancein,119-120,121,123-124renin-angiotensinsystemand,130-132specificmanipulationwith,130-132transfectionefficiencyof,124-125versatilityof,130viralfusogenicpropertiesin,112-117invivogeneticengineeringwith,130-134Hydraulicconductance,210,212Hydrogel,214Hydrogelcatheter,186Hypercholesterolemia,familialadenoviralvectorfor,439-440apoEadenoviralvectorfor,437-438lowdensitylipoproteinreceptorrolein,439retroviralvectorfor,408-410,439somaticgenetherapyfor,462systemicgenetherapyfor,396,407-410,424Hyperlipoproteinemia,typeIII,419-420Hyperplasia,neointimal,293Hypertension.
SeealsoKallikrein-kininsystemepidemiologyof,455hypotensivetransgenicmousemodelof,458kallikreingenetherapyfor,449-468.
SeealsoKallikreingenetherapyfordetailedlistingskallikreinlkinintherapyfor,456-457kallikreinrolein,455,456Hypertriglyceridemia,396Hypotensivetransgenicmousemodel,458,462Hypoxia,asstimulusforangiogenesis,320-321Hypoxia-specifictranscriptionfactor,321IIdiopathicdilatedcardiomyopathyenterovirusesand,380viralmyocarditisand,378IGRP2,39-42dexamethasone-responsiveE4expressionin,42E4messengersynthesisin,41-42LacZ-expressingE11E4-deletedRAdfrom,42-44structureof,41IGRP4,39-42careof,41LacZ-expressingE11E4-deletedRAdfrom,44-47structureof,41Immuneresponsetoadenoviralvector,405,436,443tokallikreingenetherapy,467tomyoblastgrafting,340toskeletalmyoblastgrafting,colorplates,345-347,348Inflation,catheter,efficiencyand,215-216Infusasleevecatheter,184-185Insulindeficiency,398Insulingrowthfactor-I,144Interleukin-1,144Internalribosomafentrysite,12Intramuraldelivery,491-492.
SeealsoCatheter(s)Intramuraldrugtherapy.
SeeCatheter(s)Intramuralretention,193-194Invivogenetherapy,4,26,71,89,401.
SeealsoAntisensestudies,invivowithadenoviralvectors,433-445,435-436direct,270-272withHVJ-liposomedelivery,4,26,71,369,401withkallikreingene,466-467methodsin,466withplasmidvector,404vs.
exvivo,369,400,425vs.
invitro,89,92Ischemicheartdiseaseepidemiologyof,357Kmyoblasttransfertherapyfor.
SeeMyoblasttransfertherapyKallidin,453Kallikrein(s)administrationof,456-457depressorfunctionof,453-454inessentialhypertension,455functionof,449-450,451hormoneresponsivesitesingenesof,450-451inhypertension,456regulationof,450-451typesof,449Kallikreinbindingproteins,451Kallikreingenetherapy,449-468.
SeealsoKallikrein;Kallikrein-kininsystemalbuminpromoterexpressionin,461DNAconstructsfor,457-458,459ingeneticallyhypertensiverats,462-466hypotensivetransgenicmousemodelfor,4581Mdeliveryof,463-465immuneresponseto,467IPdeliveryof,465-466IVdeliveryof,464-465liver-targeteddeliveryof,465MREpromoterexpressionin,459-461nativepromoterexpressionin,462problemswith,467significanceandfutureprospectsfor,468somatic,462-467inspontaneouslyhypertensiverat,463-464Kallikrein-kininsystem,451-452renin-angiotensinsystemrelationsof,453-454vasodilatingeffectsof,453Kallistatin,451Keratinocytesasretroviralvectors,405systemicgenetherapywith,399,403,425Kinases,cellcycledependent,147KininaseII,453Kininsbiologicaleffectsof,450forhypertension,456-457pharmacodynamicsof,456receptorsfor,450LLabeling,antibody,229Labellingindex,299-300Lactatedehydrogenasecardiacisoformof,335skeletalisoformof,335-336Lipaseoverexpression,397Lipiddisordersmonogenic,396-397systemicgenetherapyfor,396-397LipidsinDNAdelivery,96-101purityof,122Lipofection,96-101Lipoprotein,highdensityapoAIeffecton,438functionof,438Lipoproteinreceptor.
SeeHypercholesterolemia,familialLipoproteinreceptor,lowdensityadenoviralvectordeliveryof,439-440cholesterol7a-hydroxylaseand,439infamilialhypercholesterolemia,439functionof,439511genetherapyexperimentswith,407-409reductionin,441systemicgenetherapywith,401Liposomes,125-126Liposomes,cationic,97,103-104efficacyofuptakein,125-126Liposometransfectionsystems,HVJ-liposome,111-136.
SeealsoHVJ-liposomedeliverysystemfordetailsLiver,vectoraccumulationin,435LNvectors,11Localdelivery.
SeeDelivery,localLowdensitylipoproteinreceptor.
SeeHypercholesterolemia;Lipoproteinreceptor,lowdensityLymphoidcells,67-68Lysosomaldegradation,95MMajorlatepromotor(MLP),35Majorlatetranscriptionunit(MLTU)inE4deletionmutants,35-36functionof,35Masstransferconvective,486-488,491diffusive,486,488-491Messageabundance,153Metallothioneingene,459-461Metal-responseelementpromoter512inkallikreingenelcDNAconstructs,457-458,459metallothioneingeneexpressionwith,459-461Methylphosphonate,149-150MFGvector,12Microporousballooncatheter,185,203-204efficiencyof,207-216.
SeealsoCatheterefficiencyfordetailedlistingsfluiddynamicsin,206-207Microporouscatheters,vs.
porous,207,208Microvasculature,asgenetransfertarget,256Minimallumendiameter,297-298Monoclonalantibodies,recombinant/chimeric,181-182Multilamellarvesiclesefficacyof,122productionof,120-121Murineleukemiaretrovirusgenomeof,7,9infectiousvirionproductionin,8,10lifecycleof,7-10Murineretroviruses,6-14.
SeealsoRetroviruses,murine,fordetailedlistingsMyoblastgrafting,C2C12,338-342,348-350cellularmakeupofgraftsin,340ECGof,340-341EManalysisof,340-341graftsuccesswith,339-340historyof,338-339immunologyandhistologyof,340lactatedehydrogenaselevelsin,341sourceofmyoblastsfor,338-339Myoblastgrafting,skeletalC2(280),342-348,348-350administrationof,342angiogenesisfrom,344-345CCL-64growthinhibitionwith,343dietaryzincand,345-347,348EMandimmunologyof,colorplates,345-347graftsuccesswith,344-346historyof,342immunologicalresponseto,348myotubeformationin,362TGF-fJlexpressionwith,342-347Myoblast-mediatedgenetherapyadvantagesof,369-370animalmodelsfor,370-371CMVvs.
RSVfor,363-365definitionof,358evaluationof,370-371exvivodeliveryof,362-365withplasmidDNA,403potentialproblemsof,370successin,362-363therapeuticpotentialof,367-370Myoblastsconversionofphenotypeof,370growthandpurificationof,358intracardiacmigrationof,359asretroviralvectors,405skeletalvs.
cardiac,370systemicgenetherapywith,425Myoblasttransfertherapy,355-372advantagesof,366-367backgroundfor,357-358cardiacpotentialof,365definitionof,358earlydataon,358-365fJ-galactosidasestainingin,361-362goalsof,356inflammatoryresponseto,361myoblastgrowthandpurificationin,358-359myoblastsourcesin,366-367myocardialdeliveryin,359-360myocardialincorporationin,361-362therapeuticpotentialof,365-367Myocardialdiseaseadenoviral-mediated,379-380viraletiologyof,378Myocarditisacute,378adenoviralcauseof,historicalevidenceof,379-380adenoviralcauseof,PCRevidenceof,380-384adenovirusinchildrenwith,381,383-384diagnosticproblemswith,379-380PCRinhistopathologycorrelationof,384MyocardiumNadenoviralgenetherapyand,386-387adenovirusand,377-388.
SeealsoAdenovirus,myocardiumand,fordetailedlistingsNeedleinfusioncatheter,187Neoangiogenesis,256Neointimahyperplasiaof,293modelofgrowthof,295-297Nippleballooncatheter,186-187Nitricoxidesynthase,245Nonviralvectors,85-105calciumphosphatecoprecipitationdeliveryof,94DEAE-dextrandeliveryof,93-94deliveryof,92-102deliveryof,earlymethodsof,93-94deliveryof,electroporationin,94-95deliveryof,lipid-mediated,96-101.
SeealsoTransfectionreagents,lipidbaseddeliveryof,receptor-mediatedendocytosis,95-96,103-104deliveryof,StarburstDendrimer,101-102optimizationforcelltypeswith,92-93toxicityof,93invivovs.
invitroefficacyof,92N2vector,11o"Oligonucleotidereceptor,"151Oligonucleotides,148cellentryof,151-152chemicalmodificationofbackboneof,149-150chemistryof,149-151ininactivationofgeneexpression,125-127proteinsynthesisinterruptionby,152-153Oligonucleotides,antisensec-myc,161-163exactsequenceusedin,161,163-164ininactivationofgeneexpression,125-127modeofdeliveryin,164-166Oligonucleotidetechniques,antisense,147-156.
SeealsoAntisenseoligonucleotide.
.
.
fordetailedlistingsORF3,E4,35-37ORF6n,E4,38-39ORF6,E4,35-37Orificemediatedjeteffects,205pPackagingcells,11,12-13293cellline,26-27PAMAMcascadepolymers,101-102Parkinson"sdiseaseAAV-basedgenetherapyfor,69-70fetaltissuegraftsfor,333PCNA,146,147mRNA,165-166PDGFBgenecelltypestransducedby,241expressionof,240-243functionof,240immunohistochemistrystudiesof,241-242intimaformationfrom,242-243invivoeffectsofexpressionof,241-242Penetrationdepth,203Percutaneoustransluminalcoronaryangioplasty(PTCA),179-180restenosiswith,179-180Pericardialinstillation,492-493Perivasculardelivery,491-493Pharmacokinetics,localvascularvector,477-493indiseasedvessels,484-485efficiencyof,478-480localpermeationin,484optimizationof,481-485specificityof,481-482systemicdeliveryin,482-483terminologyof,478-479Phosphorthioates,150Picomaviruses,378Placentagrowthfactor,323-324Plasmidvectors.
SeeVectors,plasmidPlasminogenactivatorinhibitor-I,264Plateletderivedgrowthfactor,143-144polyclonalantibodyto,181PlateletderivedgrowthfactorBBincytokinesynergism,321endothelialcelleffectsof,319-320smoothmusclecelleffectsof,320Poliovirus,378Polyethyleneglycolcoating,231Poly(lactide-co-glycolide)microspheres,226-227Polymerasechainreaction(PCR)inanalysisofpost-transplantationrejection,381-382fordetectingadenovirus-mediatedmyocardialdisease,380-384inmyocardialvirushistopathologycorrelation,384forviraldetection,380513vs.
cultureandserology,inmyocarditis,381Polymergelsqualityandconsistencyof,167insustained-releasedelivery,224-225Polymermicrospheres,225-228membrane-freeintracellulardeliveryof,226-228Polymernanospheres,polyethyleneglycolcoatingof,231Populationdoublingtime,298-301Porouscatheters,183-184,203-205safetyandefficacyof,204-205vs.
microporous,207,208Pressureatballoon/arteryinterface,211atdrugdeliveryinterface,214flowrateand,212-214transmural,210Pressure-augmenteddiffusion,214514Pressuregradients,catheterefficiencyand,210Prodrug,478,493Producercells,11,12-13Promotersalbumin,461cell-specific,intargeteddelivery,228metal-responseelement,457-458,459-461plasmid,87tissue-specific,88viral,87ProteinCdeficiency,397Proteindeficiencies,398-399Proteindelivery.
SeeDelivery,proteinProteinexpression,86ProteinSdeficiency,397Proteoliposome,118RRatcarotidinjurymodel,156-157Receptor-mediatedendocytosisdelivery,95-96,103-104Recombinantadenoviruses,25-50.
SeealsoAdenoviruses,recombinant,fordetailedlistingsReflectance,solute,484Renin-angiotensinsystemkallikrein-kininsystemrelationsof,453-454roleinhypertensionof,453-454REPRprotein,441-442Restenosis,179-180,194causeof,293cellkineticsin,295-297cellproliferationin,293-294genetherapyfor,301-302mathematicalmodelingof,295-298,302-303minimallumendiameterand,297-298Rbexpressionand,249Reticuloendothelialsystem,Iiposomeuptakeby,103Retinoblastomagene,248-249Retrovirusesclassificationof,6-7Retroviruses,murine,6-14characteristicsof,6typeC,molecularbiologyof,7-10Retroviruses,murinereplication-deficientconstructionof,10-11developmentof,10-14geneticcomponentin,10-11Retrovirusvectors.
SeeVectors,retroviralRibonucleicacid,lipid-mediateddeliveryof,96RNaseH,153RNAtranslation,blockingof,127sSequenceselection,147-149Serumproteindeficiencies,410-424Singlechainurokinaseplasminogenactivator,261SINvectors,12Site-specifictherapy.
SeeCatheter(s);Delivery,localSkeletalmyoblastgrafting,C2(280)transfected.
SeeMyoblastgrafting,skeletal,fordetailsSmoothmuscle,vascular,70-71Smoothmusclecellgenetransfer,279-288applicationsof,280-281inarterialintima,287intoballoon-injuredartery,282-283cellcharacteristicsin,279-280factorslimitinguseof,280futureapplicationsof,286-288improvementsrequiredin,286-287nonratanimalstudiesof,285-286ratstudiesof,281-285instudyinginhibitorfunction,287-288Smoothmusclecellproliferationinhibitionof,293-294inrestenosis,293SmoothmusclecellsbFGFasmitogenfor,324controlofproliferationof,144-145,147functionof,279-280growthfactorsfor,144longlifeof,280proliferativeresponseof,143-144replicationof,aftervascularinjury,128Solutefluxrate,487Solutereflectance,484Somaticgenetherapy,462,466-467Splicingvectors,12StarburstDendrimers,10I-I02Stentedballooncatheter,186Sustained-releasegenedelivery,224-228Switchvariants,isotype,182Symbols,495Systemicgenetherapy,395-425TTangentialwallstress,211Targetedgenedelivery,228-231antibodiesandgrowthfactorsin,228labelingin,229percentofdosedeliveredin,230-231targetcellspecificityin,230Targetvessel,494TGF-/31gene,240,243-244functionof,243-244genetransferof,244Thrombophilia,397Thrombosis,localized,397-398Thymidinekinasegene,246-248Tissueplasminogenactivator,181,260-262Transactivators,transcriptional,88Transcriptionfactordecoys,128-129,133Transduction,retroviral,improvedefficiencyof,260Transductionefficiency,480Transfection,HVJviralenvelope-mediated,115-117.
Transfectionreagentslipid-based,clinicaltrialsof,100-101lipid-based,commerciallyavailable,97-98,99lipid-based,other,98,100StarburstDendrimers,101-102Transferrin,95-96Transferrinreceptor,96Transforminggrowthfactorbeta,144angiogenicactivityof,320incytokinesynergism,321Transgeneexpression,durationof,26-28Transmuralfluidflux,211Transmuralpressure,210Transportcatheter,185Transvasculardelivery,491-492T7RNApolymerase,90-91Tumorcellgrowthvdoublingtimesin,298-299labellingindicesfor,299-300Vasavasora,deliveryinto,191-192Vasculardisease,animalmodelsof,240Vascularendothelialgrowthfactor,243,308arterialtransferof,312-314collateraldevelopmentfrom,318enhancedcollateralflowwith,368hypoxicstimulationof,320-321improvedendothelium-dependentflowwith,312isoformsof,313-314mitogeniceffectsof,318secretionsignalin,313-314synergismwithbFGFof,321-324therapeuticpotentialof,309-310Vascularendothelium,70Vascularinjury,pressure-related,203Vascularpermeabilityfactor,309,318.
SeealsoVascularendothelialgrowthfactor515Vascularsmoothmuscle,70-71Vasomotortone,endothelium-dependent,311-312Vectors,3-105.
Seealsospecifictypesandapplicationsadeno-associatedviral.
SeeAdeno-associatedvirusvectorsAvl,17-20Av2,20Av3,20-21DNAvirus,57-76.
SeealsoAdeno-associatedvirusvectors;DNAvirusvectorsfordetailedlistingsdouble-copy,12endothelialcells.
SeeEndothelialcellgenetransferfordetailedlistingsGl,11-12herpessimplexvirus,221-222hostinteractionsof,21humanadenovirus,17-21LN,IImechanical,477MFG,12molecular,477N2,11SIN,12splicing,12Vectors,adeno-associatedviral.
SeeAdeno-associatedvirusvectorsVectors,adenoviral,4-6,221.
SeealsoGenetherapy,adenovirus-mediated,andspecificdisordersadvantagesof,434,442withaI-antitrypsin,410-412withapolipoproteinAI,438-439withapolipoproteinBmRNAeditingprotein,441-442withapolipoproteinE,437-438cardiovascular-relatedgenedeliverywith,436-442withcholesterol7a-hydroxylase,440-441forchronicconditions,444cytopathiceffectof,263-264,272witherythropoietin,420-422,425withFactorIX,414,416,418-419withFactorVIII,415forfamilialhypercholesterolemia,439-440ingenetransfer,25-28hepatotoxicitywith,435-436immunerejectionofcellswith,405,436,443improvementof,25-50forkallikreingene,467limitationsof,443-444liveraccumulationof,435516withlowdensitylipoproteinreceptor,439-440myocardialdiseasefrom,378myocardialdiseasefrom,animalmodelsof,385myocardialdiseasefrom,historicalevidenceof,379-380myocardialdiseasefrom,PCRevidenceof,380-384myocardialdiseasefrom,PCR-histopathologycorrelationwith,384inmyocardialgenetherapy,386-387myocardialresponseto,386-387readministrationof,444regulationofexpressionwith,442-443sizeof,221forsystemicexpression,433-445systemicgenethempywith,404--405systemicvs.
localdeliveryof,483toxicityof,444transientexpressionwith,443invivogenethempywith,404--405,435-436,442invivovs.
exvivodeliveryof,369vs.
Iipofectin,192Vectors,geneattachmentandinternalizationof,484efficacyof,celltypespecificityof,402-406efficacyof,factorsin,402-403forendothelialcellgenetransfer,257endovasculardeliveryof,485-491intramuralandperivasculardistributionof,484ratesoftranslocationof,491forsmoothmusclecelltransfer,281,282Vectors,nonviml,85-105genedeliveryvia,222-224molecularconjugatesof,223Vectors,plasmid,85-92.
SeealsospecificdisorderswithaI-antitrypsin,410-412backbonechangesin,88constructionof,87-92deliveryof,viadirectinjectionofnakedDNA,102efficacyof,402-404witherythropoietin,420-422exvivogenetherapywith,404withFactorIX,414-415withFactorVIII,415withhumangrowthhormone,422-423integrationof,90forkallikreingene,464-465mechanismsof,86-87obstaclesto,90-91quantityof,89systemicgenethempywith,403-404toxicityandpurificationof,89-90invivogenetherapywith,404invivovs.
invitrodeliveryof,89Vectors,retroviral,4-6,7,221.
Seealsospecificdisordersadvantagesof,405withaI-antitrypsin,411-413,424-425celltypeefficacyin,406efficacyof,403endothelialcelltransfervia,260exvivogenetherapywith,405exvivovs.
invivoapproacheswith,425withFactorIX,416-419,424-425withFactorVIII,415forfamilialhypercholesterolemia,408-410,439withhumangrowthhormone,422-424limitationsof,7-8forsmoothmusclecellgenetransfer,281,282systemicgenethempywith,405-406utilizationof,14VEGFexpressing,368Vectors,viralanimalmodelsofvasculardiseasefor,240artificial,103-105basicstudiesandapplicationsof,239-250cellgrowthmodificationwith,245-249deliverymethodswith,221-222designof,5-(jFGF-lgeneand,243geneticengineeringof,104-105limitationsof,86,221nitricoxidesynthaseand,245PDGFBgeneexpressionand,240-243replication-deficient,5safetyof,222TGF-jJlgeneand,243-244vascularACEgeneexpressionand,244Vimlcapsidproteins,223,226wWallstress,tangential,211Wolinskycatheters,183-184,203-205safetyandefficacyof,204-205