CRISPR for Cure
CRISPR 治愈
基本信息
- 批准号:10469440
- 负责人:
- 金额:$ 480.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-16 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AchievementAcquired Immunodeficiency SyndromeAddressAdenovirus VectorAdenovirusesAnimal ModelB-LymphocytesBar CodesBasic ScienceBiodistributionBiological AssayBiological Response Modifier TherapyBiotechnologyCCR5 geneCRISPR/Cas technologyCell MaintenanceCell physiologyCellsChromosomesClinicalClustered Regularly Interspaced Short Palindromic RepeatsCommunitiesComplementDNADNA IntegrationDNA Modification ProcessDevelopmentDiseaseDisease remissionEducation and OutreachEffector CellEpigenetic ProcessExcisionFCGR3B geneFunding AgencyFutureGenesGenetic VariationGenomeGenomicsGoalsGovernmentGranulocyte-Macrophage Colony-Stimulating FactorGrowthGuide RNAHIVHIV InfectionsHIV-1Hematopoietic stem cellsHistopathologyHumanIL3 GeneImmuneImmune responseImmune systemImmunodeficient MouseImmunologicsInfectionInterleukin-15Interleukin-6InterruptionKnock-outKnowledgeLymphoidMacacaMacaca mulattaMacrophage Colony-Stimulating FactorMeasuresMediatingMethodsModificationMolecularMonitorMorbidity - disease rateMouse StrainsMusMyeloid CellsMyelopoiesisNatural Killer CellsOutcomePatientsPeripheral Blood Mononuclear CellPersonsPopulationPositioning AttributePrivate SectorProvirusesResearchResidual stateResourcesRoleSIVSafetySamplingSpecificityStandardizationStructureT-LymphocyteTechnologyTestingThrombopoietinUp-RegulationViralViral reservoirViremiaVirusWorkantiretroviral therapybasebioinformatics pipelinecell killingclinical investigationclinical toxicologycohortcollaboratorycommunity engagementcytokinedesignexhaustionexperiencefunctional restorationgenetic approachgenome editinghigh throughput screeninghumanized mouseimmune activationimplementation barriersin vivoindustry partnerinnovationinsightlatent infectionlatent virus activationmortalitymouse modelmultidisciplinarynext generationnext generation sequencingnovelnovel strategiesoperationpre-clinicalprogrammed cell death protein 1programsresponsesynergismtranscriptomicstranslational scientistviral DNAviral reboundvirus genetics
项目摘要
While antiretroviral therapy (ART) has dramatically reduced HIV disease morbidity and mortality, it has failed to
eliminate viral reservoirs. Interruption of treatment leads to activation of latent virus and rebound viremia within
weeks. Novel strategies are urgently needed to eradicate latent infections and enhance the immune system
leading to sustained, durable control of viral rebound following the cessation of ART. In response to RFA-AI-
20-035 Martin Delaney Collaboratories for HIV Cure Research, we now submit the application entitled
"CRISPR for Cure." The overarching goal of this program is to use genome editing mediated by CRISPR to
enhance immune responses and directly ablate HIV proviruses. We have assembled a collaborative team of
highly accomplished basic and translational scientists working in tandem with community stakeholders and a
small biotechnology company to develop CRISPR-based therapies to directly target the HIV provirus and to
enhance immunological responses. The research program is comprised of three highly interactive research
foci (RF) that will utilize interdisciplinary, innovative and collaborative research approaches with community
and government input. RF1 will use next generation sequencing and novel barcoded viruses to define the HIV
reservoir and the impact of epigenetic mechanisms on proviral rebound. In RF2, we will enhance effector NK
and CTL cell function and killing and limit viral spread by target cells using innovative genome editing
strategies. RF3 will create and test the next generation of inducible, multiplex CRISPR with increased
specificity, potency and safety for delivery by CD4 tropic lymphoid AAV9 for eradication of HIV-1 proviral DNA
in animal models whose immune cells are modified in RF2 and assess the possibility of both a universal and
personalized CRISPR in eliminating replication competent virus in vivo. In addition to the shared focus on
CRISPRs technology, the Collaboratory will undertake a highly integrated experimental agenda through the
shared use of barcoded viruses in humanized mice and unique
support
MISTRG humanized mice that differentially
human hematopoietic stem and progenitor cell maintenance and myelopoiesis;rhesus macaques
infected with a novel SIV barcoded virus; ex vivo clinical samples from a well characterized cohort and the use
of adenoviruses to efficiently deliver CRISPRs to an in vivo humanized animal model carrying cells from
patient-derived PBMCs. The outcome of this comprehensive and multidisciplinary program by the “CRISPR for
Cure”
the
Collaboratory, will accelerate the use of gene editing strategies towards eradication of HIV infection from
body or sustained viral remission following cessation of antiretroviral therapy.With resources available
from our private sector partner, we will be well positioned for further GMP manufacturing development, and
future initial clinical investigations.
虽然抗逆转录病毒疗法(ART)大大降低了艾滋病毒发病率和死亡率,但它未能做到这一点
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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Tricia Helen Burdo其他文献
Tricia Helen Burdo的其他文献
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{{ truncateString('Tricia Helen Burdo', 18)}}的其他基金
Role of caspase-1 activation in HIV-1 associated atherogenesis
Caspase-1 激活在 HIV-1 相关动脉粥样硬化形成中的作用
- 批准号:
10162645 - 财政年份:2018
- 资助金额:
$ 480.77万 - 项目类别:
Role of caspase-1 activation in HIV-1 associated atherogenesis
Caspase-1 激活在 HIV-1 相关动脉粥样硬化形成中的作用
- 批准号:
9923758 - 财政年份:2018
- 资助金额:
$ 480.77万 - 项目类别:
Role of caspase-1 activation in HIV-1 associated atherogenesis
Caspase-1 激活在 HIV-1 相关动脉粥样硬化形成中的作用
- 批准号:
9751953 - 财政年份:2018
- 资助金额:
$ 480.77万 - 项目类别:
Monocyte/macrophage traffic and peripheral nerve pathogenesis
单核细胞/巨噬细胞交通和周围神经发病机制
- 批准号:
9088512 - 财政年份:2012
- 资助金额:
$ 480.77万 - 项目类别:
Monocyte/macrophage traffic and peripheral nerve pathogenesis
单核细胞/巨噬细胞交通和周围神经发病机制
- 批准号:
8467482 - 财政年份:2012
- 资助金额:
$ 480.77万 - 项目类别:
Monocyte/macrophage traffic and peripheral nerve pathogenesis
单核细胞/巨噬细胞交通和周围神经发病机制
- 批准号:
8666090 - 财政年份:2012
- 资助金额:
$ 480.77万 - 项目类别:
Monocyte/macrophage traffic and peripheral nerve pathogenesis
单核细胞/巨噬细胞交通和周围神经发病机制
- 批准号:
8554929 - 财政年份:2012
- 资助金额:
$ 480.77万 - 项目类别:
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