Therapeutic applications of adenoviruses

Adenovirus Biology and Development as a Gene Delivery VectorINTRODUCTIONAd BIOLOGYAd Virion StructureThe Ad GenomeAd InfectionFIRST-GENERATION Ad VECTORSThe First Ad VectorsE1-Complementing Cell LinesThe Problem of Replication-Competent AdMethods for Generation of E1-Deleted Ad VectorsE1-Deleted Ads in Gene TherapyLimitations of E1-Deleted Ad VectorsMULTIPLY-ATTENUATED AdsHELPER-DEPENDENT AdsONCOLYTIC Ad FOR CANCER-DIRECTED THERAPYHUMAN CLINICAL TRIALS UTILIZING Ad-BASED VECTORSAd-MEDiATED Clinical Trials for CancerAd-MEDiATED Clinical Trials for Vascular DiseaseAd-OTCCONCLUDING REMARKSREFERENCESInnate and Adaptive Immune Responses to AdenovirusADAPTIVE IMMUNITYHumoral Immune ResponseCellular ImmunityINNATE IMMUNITYAd Vector Interactions with Components of the BloodCoagulation FactorsComplementDefensinsBlood CellsAd Interactions with Liver MacrophagesAd Interactions with Spleen MacrophagesAd Interactions with Lung MacrophagesREFERENCESHelper-Dependent Adenoviral Vectors for Cell and Gene TherapyINTRODUCTIONHDAd PRODUCTIONINTRACELLULAR STATUS OF HDAd VECTORSEX VIVO GENE TRANSFERHDAd and Stem CellsEx vivo Gene Transfer in Dermal FibroblastsIN VIVO GENE THERAPYLiver-Directed Gene TherapyLung Gene TherapyGene Therapy for Brain, Eye, and Muscle DisordersCONCLUSIONSREFERENCESChemical and Combined Genetic and Chemical Modifications of Adenovirus Vector Capsids to Overcome Barriers for In Vivo Vector DeliveryINTRODUCTIONAd Vectors and Gene TherapyBASIC Ad BIOLOGYClassificationStructureCell Entry In VitroVirus Genome and Life CycleTypes of Ad VectorsBARRIERSInteractions with Blood Coagulation FactorsInteractions with Natural Antibodies and Complement: Factor X as a Natural Shield against Attack by ComplementSequestration by Kupffer Cells, Liver Sinusoidal Endothelium and PlateletsSequestration by ErythrocytesInnate Immune Activation and Acute ToxicityAcquired Anti-Vector Humoral ImmunityDemands for an Ideal Ad VectorSTRATEGIES AND TECHNOLOGIES TO OVERCOME BARRIERSChemical Capsid ModificationsChemical Capsid Modifications with Synthetic PolymersPolyethylene GlycolPoly(N-(2-Hydroxypropyl)Methacrylamide)Polymer Shields Can Dampen the Induction of Innate Immunity, Toxicity, and Adaptive Immune ResponsesHumoral Anti-Vector Immunity and the Complement SystemBlood Coagulation Factor Binding and Hepatocyte TropismDefined Attachment of Shielding Polymers to Selected Capsid SitesSequestration by Immune Cells, Platelets and Liver Sinusoidal EndotheliumVector Sequestration by ErythrocytesSYNOPSISREFERENCESDesign and Applications of Adenovirus-Based Hybrid VectorsINTRODUCTION: DEFINITION OF ADENOVIRUS-BASED HYBRID VECTORSMOLECULAR DESIGN AND APPLICATIONS OF Ad-BASED HYBRID VECTORSHybrid Vectors for Somatic Integration Into Host ChromosomesThe Ad-Transposase Hybrid Vector SystemThe Ad-Integrase Hybrid Vector SystemAd/AAV-Rep Hybrid VectorsHybrid Vectors for Episomal Persistence of Foreign DNAAd/pEPI Hybrid VectorsAd/EBV Hybrid Vector SystemsAd/SFV Hybrid VectorsHybrid Vectors for Site-Specific Genome EditingHybrid Adenoviral Vectors for Viral Vector ProductionHybrid AdV/Retrovirus System for Retroviral Vector ProductionHybrid AdV Systems for Lentiviral Vector ProductionHOW TO CHOOSE THE RIGHT Ad-BASED HYBRID VECTOR?REFERENCESAdenovirus Vectors for Genome Editing Involving Engineered EndonucleasesGENOME ENGINEERING IN STEM CELLS: OVERVIEWTarget CellsSite-Specific DNA Breaks Mediated by EndonucleasesGene Targeting by Homology Directed Repair Involving Donor VectorsADENOVIRUS VECTORS FOR GENOME EDITING-ADVANTAGESGene Delivery to Nondividing CellsNon-Integrating Nature of Most Ad SerotypesInsert CapacityCapsid Modification to Improve Tropism to Target CellsIn Vivo ApplicationCost of Vector ManufacturingADENOVIRUS VECTORS FOR GENOME EDITING—DISADVANTAGESCytotoxicity of First-Generation Vectors in Stem CellsLoss of EN Expression Cassettes from Viral Genomes During Ad Vector ProductionCytotoxicity Associated with Extended EN ExpressionADENOVIRUS VECTOR FOR GENOME EDITING-EXAMPLESEN-Based Antiviral TherapiesGene Targeting in Cell Lines and Immortalized Primary CellsGenome Editing in iPS Cells to Introduce or Correct Disease MutationsGenome Editing in HSCsGenome Editing in MSCsIn Vivo Genome EditingREFERENCESAdenoviruses for VaccinationINTRODUCTION: BACKGROUND AND DRIVING FORCESInactivated/Attenuated Pathogen VaccinesProtein VaccinesGenetic or DNA Vaccines or Gene-Based VaccinesPrime-Boost Combinations of Gene-Based and Protein-Based VaccinesViral Vectors as Gene-Based VaccinesAdenoviruses as VaccinesAccidental Proof of Principle for the Use of Ads as Gene-Based VaccinesAds as Gene-Based VaccinesADPPLES AND ORANGESAd VECTORS WITH DIFFERENT DNA AND VIRUS REPLICATION CAPACITIESRC-Ad Vaccines Amplify Antigen TransgenesRC-Ad Vaccines Amplify Infectious Progeny Viruses and Can Risk Adenovirus InfectionsRD-Ads: First Generation AE1, АБ3 VectorsRD H elper-Dependent Ad Vectors to Evade Vector-Specific Т-Cell ResponsesH ead to Head Comparisons of RC and RD-Ad VaccinesH ead to Head Comparisons of RC, RD, and HD-Ad VaccinesSingle-Cycle Ad Vaccines: Transgene Replication without Virus ProductionAmplified Production of Functional Influenza Antibodies by SC-AdPRE-EXISTING AND VECTOR-INDUCED ANTI-Ad IMMUNE RESPONSESInnate Immune ResponsesТ-Cell ResponsesNeutralizing AntibodiesComparison to Other Vaccine PlatformsEVADING IMMUNE RESPONSES AGAINST Ad VECTORSHD-Ad Vectors to Evade Vector-Specific Т-Cell ResponsesUse Lower Seroprevalence Ads to Avoid Pre-Existing Ad Antibodies in HumansSerotype Switching to Evade Vector- Induced Neutralizing AntibodiesPEGylation to Evade Pre-Existing Neutralizing Antibodies and Reduce Adaptive Antibody and Cellular Responses against Ad VectorsExamples: Serotype-Switching HD-Ad HIV VaccinesPEG versus Serotype SwitchingOPPORTUNITIES AND CHALLENGESChallenges: Bad Public Relations: The HIV STEP Vaccine TrialReality CheckOpportunity: An Improving RD-Ad Vaccine Result LandscapeOpportunity: RD-Ad Moved Forward for Ebola Virus Vaccination in HumansAdpples and Oranges Challenge: VSV Ebola Vaccine versus RD-Ad Ebola Vaccine?Opportunity and Challenge: RC-Ad VaccinesREFERENCESUse of Oncolytic Adenoviruses for Cancer TherapyINTRODUCTIONCancerCurrent TherapiesHISTORY OF OAdsOncolytic AdenovirusesExploiting the Lack of Cell Defense Mechanisms (Biological Targeting)Cancer Promoter-Dependent OAds (Transcriptional Targeting)Armed OAdSuicide Gene Therapy by AdenovirusesExpression of Immune ModulatorsCapsid Modification of OAds (Transductional Targeting)CURRENT TRENDS IN ADENOVIRAL VECTORS FOR CANCER THERAPYToward Oncolytic VaccinesOAds in Combination with Other TherapiesCombination with ChemotherapyCombination with RadiotherapyCombination with ImmunotherapyCONCLUSIONSREFERENCES
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