Research and Development to Establish a Small Animal Model as a Significant Resource of High-Value Single-Domain Antibodies
建立小动物模型作为高价值单域抗体重要资源的研发
基本信息
- 批准号:10481556
- 负责人:
- 金额:$ 99.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-03-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AffinityAlpacaAnimal ModelAnimalsAntibodiesAntibody AffinityAntibody FormationAntibody ResponseAntigensAutoantigensB-Cell DevelopmentBacteriaBasic ScienceBenchmarkingBindingBiologicalBiological ProductsBiotechnologyBreedingBusinessesCamelsCellsCharacteristicsClientClinicalComplexCoupledCustomDevelopmentDiagnosticDiagnostics ResearchDiseaseEngineeringEnterobacter cloacaeEpitopesFab ImmunoglobulinsFutureGene BankGene ProteinsGene TargetingGenerationsGenesGeneticGenetic EngineeringGenetically Engineered MouseGoalsHIVHIV Envelope Protein gp120Homer 1HousingHumanHybridomasHybridsImmuneImmune responseImmunizationImmunizeImmunoglobulinsIn VitroIndividualLaboratoriesLicensingLightLight-Chain ImmunoglobulinsLinkLlamaLogisticsMalignant NeoplasmsMedicineMembraneModelingMusNatural SelectionsNatureOutcomePerformancePhage DisplayPharmaceutical PreparationsPharmacologic SubstancePhasePhenotypePlayProcessProductionPropertyProteinsProtocols documentationResourcesRoleSARS-CoV-2 spike proteinServicesSharkSmall Business Innovation Research GrantTargeted ResearchTechnologyTestingTherapeuticTherapeutic AgentsVirusYeastsanimal resourceantibody diagnosticantibody librariesantigen bindingbaseclinical applicationclinical diagnosticscohortcostembryonic stem cellenvironmental stressorexperimental studyflexibilitygenetic manipulationhybrid antibodyhydrophilicityimmunogenicityimprovedin vivoin-vivo diagnosticsinterestmouse modelnanobodiesneutralizing antibodynovelpathogenpathogenic microbepreservationresearch and developmentsensorstandard of carevalidation studiesvirus host interaction
项目摘要
Project Summary
Genetically-modified mouse models have proven to be essential for the production of antibody-related
biological drugs (biologics). To date, the majority of biologics originate from mouse models, and small animal
models are used not only to generate the antibodies, but also as a platform for further optimization and testing
of the biologics. Camelid-based antibodies, which have superior antigen binding and physicochemical
properties (stability, hydrophilicity, etc.) have not realized their full potential, to the same extent that
conventional antibodies have. This is founded in the logistic and financial hurdles immunization of camelids
pose for monoclonal heavy-chain antibody (HCAb) production and the fact that in vitro technologies cannot
fully recapitulate the exceptional natural selection towards extremely diversified, high-affinity binders that
occurs in animals. In this SBIR project we propose to develop genetic platforms in a murine host for the
discovery and development of partially humanized hybrid HCAbs (and their products). Since their discovery in
the early 1990s, HCAbs have generated progressive interest in the biotech, diagnostic and therapeutic fields
due to their intrinsic properties and adaptability. Apart from a small size paired with robustness and superior
access to difficult epitopes, HCAbs can be easily processed into, and utilized as, single domain binding units
(VHH) while preserving their affinity towards antigens (in contrast to conventional antibodies). The proposed
targeted mouse models carrying an engineered immunoglobulin locus will potentiate the production of high
affinity HCAbs by serving as an alternative, hybrid Ab host. It will allow natural, in vivo affinity-maturation of
antigen-specific HCAbs in a small animal platform, one amenable to further genetic manipulation. It will enable
larger cohort sizes than the natural camelid hosts, and streamline HCAb generation, thus providing further
potential for the development of HCAb and VHH domains for downstream applications. In our Aim 1, we focus
on honing and characterizing our hybrid camelid immunoglobulin locus by adding more camelid VHHs and
introducing modified human VHs into the locus while also evaluating B-cell development and antibody affininty
and diversity. In Aim 2, our focus is to benchmark the the repertoire and efficiency of the Ab response with
competing technologies by using disease-relevant, difficult antigens and progress promising hits to hybridoma
development and larger scale antibody production. In accomplishing these milestone based Aims, we will be
able to develop our business and begin licensing of the platforms to individual labs and established
pharmaceutical companies to support discovery of novel antibodies for high-value targets.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Milen Kirilov其他文献
Milen Kirilov的其他文献
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{{ truncateString('Milen Kirilov', 18)}}的其他基金
Business Potential of a Novel Small Animal Model and its Single-Chain Antibodies
新型小动物模型及其单链抗体的商业潜力
- 批准号:
10087209 - 财政年份:2018
- 资助金额:
$ 99.9万 - 项目类别:
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