grant
B cells as boostable factories for HIV inhibition
Organization UNIVERSITY OF SOUTHERN CALIFORNIALocation Los Angeles, UNITED STATESPosted 5 Sept 2025Deadline 30 Jun 2030
NIHUS FederalResearch GrantFY2025AIDS VirusAcquired Immune Deficiency Syndrome VirusAcquired Immunodeficiency Syndrome VirusAllelesAllelomorphsAnimalsAntibodiesAntibody SpecificityAntibody-Secreting CellsAntigensB blood cellsB cellB cell depletion therapyB cell directed therapyB cell receptorB cell targeted therapyB cell therapiesB cell therapyB cellsB-Cell Antigen ReceptorB-CellsB-LymphocytesB-cellBBB crossingBlood Plasma CellBlood Precursor CellBone MarrowBone Marrow Reticuloendothelial SystemCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCas nuclease technologyCell BodyCell FunctionCell PhysiologyCell ProcessCell TherapyCellsCellular FunctionCellular PhysiologyCellular ProcessClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyCollaborationsConstant RegionCustomDNA cassetteDataEngineeringEnvelope ProteinExclusionFc domainFrequenciesGenesGoalsHIVHIV AntibodiesHIV Entry InhibitorsHIV InfectionsHIV therapyHIV-Associated AntibodiesHTLV-III AntibodiesHTLV-III InfectionsHTLV-III-LAV AntibodiesHTLV-III-LAV InfectionsHalf-LifeHeavy-Chain ImmunoglobulinsHematopoietic Progenitor CellsHematopoietic stem cellsHumanHuman Immunodeficiency VirusesHuman T-Lymphotropic Virus Type III AntibodiesHuman T-Lymphotropic Virus Type III InfectionsIGHIGH@ gene clusterIg Constant RegionIgH locusImmune GlobulinsImmunizationImmunoglobulin Constant RegionImmunoglobulin Heavy Chain GenesImmunoglobulin Heavy GeneImmunoglobulin Heavy LocusImmunoglobulin-Secreting CellsImmunoglobulinsInfectionInfusionInfusion proceduresInjectionsLAV AntibodiesLAV-HTLV-IIILymphadenopathy-Associated AntibodiesLymphadenopathy-Associated VirusLymphatic TissueLymphoid TissueM mulattaM. mulattaMacacaMacaca mulattaMacaca rhesusMacaqueMature B-CellMature B-LymphocyteMemoryModelingModern ManOrganoidsOutputPersonsPhenotypePlasma CellsPlasmacytesReagentRhesus MacaqueRhesus MonkeySHIVSafetySeriesSiteSubcellular ProcessSynthetic antigen binderTonsilVHHVHH antibodyVaccinatedVaccinationVirus ReplicationVirus-HIVantibody engineeringantibody mimeticsantibody-like binderantibody-like moleculeantibody-like proteinantibody-like reagentblood cell progenitorblood progenitorblood stem cellblood-brain barrier crossingblood-forming stem cellbloodbrain barrier crossingcamelid antibodycamelid based antibodycamelid derived antibodycamelid derived fragmentcamelid heavy chain only Abscamelid immunoglobulincamelid single chain antibodycamelid variable heavy chaincell based interventioncell engineeringcell mediated interventioncell mediated therapiescell-based therapeuticcell-based therapycellular engineeringcellular therapeuticcellular therapycryogelcustomsdesigndesigningenhancer cassetteenv Antigensenv Gene Productsenv Polyproteinsenv Proteinexpression cassetteflexibilityflexiblefully-deleted adenoviral vectorfully-deleted adenovirus vectorgene cassettegenetic cassettegenome editinggenomic editinggutless adenoviral vectorgutless adenovirus vectorgutted adenoviral vectorgutted adenovirus vectorhdAdhelper-dependent adenoviral vectorhelper-dependent adenovirus vectorhematopoietic progenitorhematopoietic stem progenitor cellhemopoietic progenitorhemopoietic stem cellhumanized micehumanized mouseimmunogenimmunoglobulin heavy chain locusimprovedin vitro Assayin vivoinfusionsinhibitorintegration cassettemouse modelmurine modelnanobodiesnanobodyneutralizing antibodynext generationnovelparticleplasmocytepreventpreventingprogramspromoterpromoter cassettepromotorrepairrepairedreporter cassetteresistance cassetteresponsesdAbselectable cassetteselection cassettesimian HIVsimian human immunodeficiency virussingle domain antibodiesstop cassettesynthetic antigen binding reagenttonsillartranscription cassettetranscriptional cassettetransgene cassettevariable heavy chain antibodyvectorviral multiplicationviral replicationvirus multiplication
Description preview
ABSTRACT
We are developing reprogrammed B cells to secret anti-HIV molecules. We use CRISPR/Cas9 genome editing
to precisely insert custom antibody cassettes at the endogenous immunoglobulin locus. In this way the
engineered B cells maintain the ability to respond to a matched antigen such as the HIV Env protein, and can
differentiate into both…
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