A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups
HIV基因驱动疗法:针对高危人群的单次给药干预
基本信息
- 批准号:10163412
- 负责人:
- 金额:$ 18.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-15 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVAcquired Immunodeficiency SyndromeAwardBiological AssayBioreactorsCD4 Positive T LymphocytesCOVID-19Cell SurvivalCellsClinicalCulicidaeDataDisease OutbreaksEngineeringExhibitsExposure toGeneral PopulationGenesGenomicsGoalsHIVHIV therapyHIV-1HomelessnessImprisonmentIn VitroIndividualInfectionInjecting drug userInterventionLinkLymphocyteMedicalMexicoNatureOutcomeParentsPathogenesisPathogenicityPatientsPopulationResourcesRiskRouteSymptomsT-Cell DepletionT-LymphocyteTechnologyTestingTherapeuticVaccinesValidationViralViral GenesViral Load resultViral PathogenesisVirusVirus ReplicationZika Virusantiretroviral therapybasecell killingco-infectioncohortdisease transmissionhigh riskhigh risk populationhumanized mousemedical countermeasuremeetingsmortality riskmutantnovelprotective effectsuccesstransmission process
项目摘要
PROJECT SUMMARY/ABSTRACT
For COVID-19, persons who inject drugs (PWID) have been identified as a population at high-risk of exposure
to SARS-CoV-2 (the virus that causes COVID-19) because of their increased risk of homelessness or
incarceration—situations linked to increased rates of the disease transmission and co-infection with HIV-1.
Given that a SARS-CoV-2 vaccine is likely 12–24 months away, there is a critical unmet medical need for medical
countermeasures that could contain COVID-19 outbreaks in the general population and in these difficult-to-reach
high-risk populations such as PWIDs in particular. Moreover, there is a fundamental gap in our understanding
of SARS-CoV-2 infection and pathogenesis in these at-risk PWID populations. Evidence indicates that SARS-
CoV-2 infects and depletes T lymphocytes and many HIV-infected PWID have limited access to antiretroviral
therapy and consequently exhibit pre-existing CD4+ T-cell depletion. Hence, SARS-CoV-2 infection could
accelerate clinical progression to AIDS, or alternatively, SARS-CoV-2 infection in HIV+ PWID could exacerbate
COVID-19 clinical symptoms leading to elevated risk of death. Thus, HIV+ PWID may be at elevated risk of
death from SARS-CoV-2 infection. In these PWID populations, reducing T-cell depletion would be highly
beneficial to halting clinical progression and may a viable long-term therapeutic goal. The specific objective of
this supplement proposal is to repurpose existing technologies to rapidly develop a Gene Drive Therapy (GDT)
candidate for SARS-CoV-2 and quantify its breadth of interference and transmission in vitro in patient T-cells
from HIV+ PWID. This effort will build heavily off our recent success in engineering an HIV-1 GDT (see Parent
Award) and a GDT against Zika Virus (ZIKV), demonstrating that the GDT concept can be repurposed for other
viruses. The central hypothesis—based on extensive preliminary studies in HIV and ZIKV—is that a putative
SARS-CoV-2 GDT, depleted of all the pathogenic viral genes, could target the same cells as wild-type SARS
CoV-2 (including T lymphocytes), compete for intracellular resources, and reduce SARS CoV-2 viral load and
pathogenesis, thereby serving as a single-administration therapeutic. The rationale for a GDT countermeasure
for SARS CoV-2 is based on extensive data for HIV-1 in humanized mice and positive FDA meetings. We will
achieve our objectives via two specific aims: (i) Engineer a SARS-CoV-2 GDT candidate (by adapting the existing
Bioreactor platform); and (ii) Test the SARS CoV-2 GDT candidate's protective effect on patient T-cells from an
HIV+ PWID cohort in Tijuana Mexico. While the GDT approach carries inherent risks, single-administration
therapeutics would be highly beneficial particularly for treating difficult-to-reach, high-risk PWID populations.
Regardless of the success of GDTs in protecting against T-cell depletion, the studies proposed here will have
broad fundamental significance by assaying how SARS-CoV-2 infection impacts T lymphocytes from HIV+
PWID. These studies would also provide validation of a novel medical countermeasure with the potential to be
rapidly deployed against new viral threats.
项目总结/文摘
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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Leor S Weinberger其他文献
Leor S Weinberger的其他文献
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{{ truncateString('Leor S Weinberger', 18)}}的其他基金
A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups
HIV基因驱动疗法:针对高危人群的单次给药干预
- 批准号:
10404422 - 财政年份:2021
- 资助金额:
$ 18.9万 - 项目类别:
A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups
HIV基因驱动疗法:针对高危人群的单次给药干预
- 批准号:
10596543 - 财政年份:2020
- 资助金额:
$ 18.9万 - 项目类别:
A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups
HIV基因驱动疗法:针对高危人群的单次给药干预
- 批准号:
10597282 - 财政年份:2020
- 资助金额:
$ 18.9万 - 项目类别:
A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups
HIV基因驱动疗法:针对高危人群的单次给药干预
- 批准号:
10377987 - 财政年份:2020
- 资助金额:
$ 18.9万 - 项目类别:
A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups
HIV基因驱动疗法:针对高危人群的单次给药干预
- 批准号:
10381365 - 财政年份:2020
- 资助金额:
$ 18.9万 - 项目类别:
A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups
HIV基因驱动疗法:针对高危人群的单次给药干预
- 批准号:
10782797 - 财政年份:2020
- 资助金额:
$ 18.9万 - 项目类别:
Modulating Stochastic Gene Expression for Cell-fate Control and Therapeutics
调节随机基因表达以控制细胞命运和治疗
- 批准号:
10211509 - 财政年份:2014
- 资助金额:
$ 18.9万 - 项目类别:
Modulating Stochastic Gene Expression for Cell-fate Control and Therapeutics
调节随机基因表达以控制细胞命运和治疗
- 批准号:
10581483 - 财政年份:2014
- 资助金额:
$ 18.9万 - 项目类别:
Stochastic Gene Expression in Retroviral Latency
逆转录病毒潜伏期的随机基因表达
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9285693 - 财政年份:2014
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Experiment & Theory to Test an Evolutionary Fitness Role for Lentiviral Latency
实验
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8891364 - 财政年份:2014
- 资助金额:
$ 18.9万 - 项目类别:
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