Novel AAVs Engineered for Efficient and Noninvasive Cross-Species Gene Editing Throughout the Central Nervous System
专为整个中枢神经系统进行高效、非侵入性跨物种基因编辑而设计的新型 AAV
基本信息
- 批准号:10490394
- 负责人:
- 金额:$ 135.97万
- 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:2018-09-30 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAffectAnimal TestingAnimalsAstrocytesBiological ProductsBlood - brain barrier anatomyBrainCallithrixCapsidCellsCentral Nervous System DiseasesCharacteristicsClinicalClinical TrialsClinical Trials DesignCollaborationsCommunitiesDependovirusDirected Molecular EvolutionDiseaseEngineeringEnsureEnterobacteria phage P1 Cre recombinaseEuropeEvaluationFutureGene DeliveryGene ExpressionGene Transduction AgentGene TransferGenesGeneticGenetic DiseasesGenetic ModelsHumanInjectionsIntravenousKnock-inLeadLibrariesMacaca mulattaMental disordersMethodsMethyl-CpG-Binding Protein 2Mucopolysaccharidosis IIMusNatureNeuraxisNeurogliaNeuronsPharmaceutical PreparationsPhasePopulationProductionRattusRecoveryReporterRhesusRodentSafetySomatic CellSystemTechnologyTestingTherapeuticTimeToxic effectUnited States National Institutes of HealthVariantVirusbasebody systemcell typeearly phase clinical trialgene delivery systemgene therapygenome editinggenome-wideimprovedin vivoinsertion/deletion mutationinterestintravenous administrationlead candidatenervous system disordernext generationnonhuman primatenovelpre-clinicalprogramsscale upsmall moleculesomatic cell gene editingsuccesstooltransduction efficiencytransgene expressionvectorvector genome
项目摘要
Project Summary:
Many genetic diseases that affect the central nervous system (CNS) remain untreatable due to a lack effective
small molecule drugs or biologics. Targeting the genetic underpinnings of these diseases with somatic cell gene
editing would therefore be particularly impactful, but its successful implementation will require methods to safely
and efficiently deliver genes and gene editing machinery throughout the CNS. AAVs are the state-of-the-art
vehicles for in vivo gene transfer because they can provide safe and long lasting in vivo gene expression. AAVs
are the only gene therapy vectors that have been approved for direct administration to humans by regulatory
agencies in both the US and Europe. Moreover, in 2017, AAVs became the first vehicle used as part of an early
phase clinical trial to evaluate the safety of in vivo gene editing. Despite their impressive preclinical and clinical
safety record, naturally occurring AAVs tested to date lack the efficiency required for gene delivery across most
organ systems, including the CNS. To address the need for better vehicles for CNS gene delivery, we recently
used directed evolution and a new cell type-specific in vivo selection method to engineer several novel AAVs,
most notably AAV-PHP.B and AAV-PHP.eB, that have, for the first time, made it possible to noninvasively
transfer genes to the majority of neurons and astrocytes throughout the adult mouse CNS. Here, we aim to build
upon the success of this selection approach by engineering AAVs that enable efficient gene transfer throughout
the CNS of multiple species, including nonhuman primates. The AAVs we develop will be evaluated in several
species for their ability to provide CNS-wide transgene expression and targeted genome editing in neurons, and
improved AAV variants will be shared with the scientific community. Successful completion of this project, which
involves pairing the new AAVs with next-generation gene editing technologies, will provide support for evaluating
the safety of CNS gene editing in human trials.
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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Benjamin E Deverman其他文献
Benjamin E Deverman的其他文献
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{{ truncateString('Benjamin E Deverman', 18)}}的其他基金
Novel AAV Capsids and Gene Regulatory Elements for GeneExpression in Microglia
用于小胶质细胞基因表达的新型 AAV 衣壳和基因调控元件
- 批准号:
10195876 - 财政年份:2021
- 资助金额:
$ 135.97万 - 项目类别:
Novel AAV Capsids and Gene Regulatory Elements for GeneExpression in Microglia
用于小胶质细胞基因表达的新型 AAV 衣壳和基因调控元件
- 批准号:
10376863 - 财政年份:2021
- 资助金额:
$ 135.97万 - 项目类别:
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.
开发和验证 AAV 载体,以操纵哺乳动物物种中与癫痫和精神疾病有关的特定神经元亚型和回路。
- 批准号:
9804329 - 财政年份:2019
- 资助金额:
$ 135.97万 - 项目类别:
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.
开发和验证 AAV 载体,以操纵哺乳动物物种中与癫痫和精神疾病有关的特定神经元亚型和回路。
- 批准号:
10001022 - 财政年份:2019
- 资助金额:
$ 135.97万 - 项目类别:
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.
开发和验证 AAV 载体,以操纵哺乳动物物种中与癫痫和精神疾病有关的特定神经元亚型和回路。
- 批准号:
10170428 - 财政年份:2019
- 资助金额:
$ 135.97万 - 项目类别:
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.
开发和验证 AAV 载体,以操纵哺乳动物物种中与癫痫和精神疾病有关的特定神经元亚型和回路。
- 批准号:
10612519 - 财政年份:2019
- 资助金额:
$ 135.97万 - 项目类别:
Novel AAVs engineered for efficient and noninvasive cross-species gene editing throughout the central nervous system
新型 AAV 专为整个中枢神经系统进行高效、非侵入性的跨物种基因编辑而设计
- 批准号:
10455344 - 财政年份:2018
- 资助金额:
$ 135.97万 - 项目类别:
Novel AAVs engineered for efficient and noninvasive cross-species gene editing throughout the central nervous system
新型 AAV 专为整个中枢神经系统进行高效、非侵入性的跨物种基因编辑而设计
- 批准号:
10001044 - 财政年份:2018
- 资助金额:
$ 135.97万 - 项目类别:
Novel AAVs engineered for efficient and noninvasive cross-species gene editing throughout the central nervous system
新型 AAV 专为整个中枢神经系统进行高效、非侵入性的跨物种基因编辑而设计
- 批准号:
9789390 - 财政年份:2018
- 资助金额:
$ 135.97万 - 项目类别:
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