A Novel Vector Platform to Actualize T Cell Modification In Vivo
A Novel Vector Platform to Actualize T Cell Modification In Vivo
批准号:
10663022
负责人:
David Terry Curiel
金额:
$42.76万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-08-04 至 2025-07-31
关键词:
AblationAddressAdenovirusesAdvanced DevelopmentBCAR1 geneCapsidCellsChimera organismChronicClinicalClustered Regularly Interspaced Short Palindromic RepeatsDependovirusDevelopmentDiseaseEngineeringFiberFosteringGene DeliveryGene TransferGenerationsGenesGeneticGenomeHumanImmunotherapyIn SituInterventionLiverLocalesMalignant NeoplasmsMethodsModificationMusOrganPatientsSerotypingSimian AdenovirusesSingle-Stranded DNASumSurfaceSystemT-LymphocyteTechniquesTechnologyTimeTissuesTransgenesTropismViralVirusVirus Diseasesbase editingchimeric antigen receptorchimeric antigen receptor T cellscostdesignflexibilitygene delivery systemimprovedin vivomouse modelneoplasticnovelnovel strategiesparticlepractical applicationrepairedtechnology platformtherapeutic genome editingtherapy outcometransduction efficiencyvector
中文摘要
摘要
英文摘要
ABSTRACT
To address the need for improved gene editing delivery systems, we propose constructing a chimeric “AdAAV”
vector consisting of an adenovirus (Ad) with multiple adeno-associated viruses (AAVs) conjugated to its capsid's
surface. We plan to employ the SpyTag/SpyCatcher technology to conjugate AAVs onto the Ad capsid. Of note
in this regard, Ads are able to selectively target certain tissues (such as the liver in the case of huAd5) with high
transduction efficiencies. Furthermore, our group has been able to engineer Ad fibers to facilitate tissue-specific
targeting of T cells. In addition, by choosing an appropriate AAV serotype, and/or through capsid engineering
AAVs can also selectively target desired tissues as well. AdAAVs may therefore provide superior targeting
through the combined effects of both engineered Ad fiber and AAV capsid (which are matched to target the same
tissue type). As a proof-of-concept, we plan to target T cells with AdAAVs. In addition, because AAVs carry
single-stranded DNA, they can provide single-stranded donor templates, which are known to enhance the editing
efficiency of homology directed repair (HDR). Within an AdAAV, the Cas protein can be encoded by the Ad
genome while the single-stranded DNA template can be embodied within the genome of the AAVs. By virtue of
the advantages of single-stranded donor templates for HDR, and by virtue of the high copy number of donor
templates carried by the multiple AAVs associated with each Ad, this design might substantially increase editing
efficiency. Finally, the AdAAV would possess a large packaging capacity since it would consist of a sum of the
Ad's capacity (which is already high) and the AAV's capacity. Due to these factors, we suggest that AdAAVs
may form a powerful and versatile new delivery system for gene editing therapies which overcomes many of the
limitations associated with existing approaches. Our highly original AdAAV delivery system will greatly enhance
the versatility of existing CRISPR-Cas gene editing therapies by circumventing several key obstacles to their
broader applicability. The design features of AdAAV will potentially make it an ideal vector by which to address
the challenges of gene editing delivery and thereby broadly enhance the general feasibility of gene editing-based
therapies.
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Novel Vector Platform for Gene Therapy
-
批准号:10231536
-
项目类别:
-
资助金额:$42.23万
-
财政年份:2021
-
负责人:David Terry Curiel
-
依托单位:
Endothelial-targeted adenovirus for organ-selective gene editing in vivo
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批准号:10228031
-
项目类别:
-
资助金额:$74.11万
-
财政年份:2019
-
负责人:David Terry Curiel
-
依托单位:
Novel Vector Platform for Gene Therapy
-
批准号:10388103
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项目类别:
-
资助金额:$37.01万
-
财政年份:2019
-
负责人:David Terry Curiel
-
依托单位:
Endothelial-targeted adenovirus for organ-selective gene editing in vivo
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批准号:9810634
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项目类别:
-
资助金额:$71.51万
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财政年份:2019
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负责人:David Terry Curiel
-
依托单位:
In Vivo Editing for Hemophilia Gene Therapy
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批准号:9695292
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项目类别:
-
资助金额:$21.51万
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财政年份:2018
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负责人:David Terry Curiel
-
依托单位:
A 3D IN VITRO DISEASE MODEL OF ATRIAL CONDUCTION
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批准号:10166441
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项目类别:
-
资助金额:$72.36万
-
财政年份:2017
-
负责人:David Terry Curiel
-
依托单位:
GORILLA ADENOVIRUS ZIKA VACCINE FOR HUMANS
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批准号:9316943
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项目类别:
-
资助金额:$19.06万
-
财政年份:2017
-
负责人:David Terry Curiel
-
依托单位:
A 3D IN VITRO DISEASE MODEL OF ATRIAL CONDUCTION
-
批准号:10228624
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项目类别:
-
资助金额:$106.55万
-
财政年份:2017
-
负责人:David Terry Curiel
-
依托单位:
Novel targeted adenovirus
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批准号:9511780
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项目类别:
-
资助金额:$34.88万
-
财政年份:2017
-
负责人:David Terry Curiel
-
依托单位:
Novel targeted adenovirus
-
批准号:10163752
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项目类别:
-
资助金额:$34.88万
-
财政年份:2017
-
负责人:David Terry Curiel
-
依托单位:
Novel targeted adenovirus
-
批准号:9927597
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项目类别:
-
资助金额:$34.88万
-
财政年份:2017
-
负责人:David Terry Curiel
-
依托单位:
A GENE-THERAPY BASED FUNCTIONAL RESTORATION OF SALIVARY GLANDS
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批准号:8513306
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项目类别:
-
资助金额:$18.24万
-
财政年份:2012
-
负责人:David Terry Curiel
-
依托单位:
Motor neuron-targeted adenovirus antidotes for botulism
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批准号:8469824
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项目类别:
-
资助金额:$23.15万
-
财政年份:2012
-
负责人:David Terry Curiel
-
依托单位:
A GENE-THERAPY BASED FUNCTIONAL RESTORATION OF SALIVARY GLANDS
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批准号:8390219
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项目类别:
-
资助金额:$22.8万
-
财政年份:2012
-
负责人:David Terry Curiel
-
依托单位:
Motor neuron-targeted adenovirus antidotes for botulism
-
批准号:8366687
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项目类别:
-
资助金额:$20.86万
-
财政年份:2012
-
负责人:David Terry Curiel
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依托单位:
Targeted-and Image-Based Adenovirus Cancer Therapeutic Vectors
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批准号:8520256
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项目类别:
-
资助金额:$44.9万
-
财政年份:2011
-
负责人:David Terry Curiel
-
依托单位:
Targeted-and Image-Based Adenovirus Cancer Therapeutic Vectors
-
批准号:8338807
-
项目类别:
-
资助金额:$47.28万
-
财政年份:2011
-
负责人:David Terry Curiel
-
依托单位:
Targeted-and Image-Based Adenovirus Cancer Therapeutic Vectors
-
批准号:8894446
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项目类别:
-
资助金额:$46.95万
-
财政年份:2011
-
负责人:David Terry Curiel
-
依托单位:
Targeted-and Image-Based Adenovirus Cancer Therapeutic Vectors
-
批准号:8183787
-
项目类别:
-
资助金额:$51.79万
-
财政年份:2011
-
负责人:David Terry Curiel
-
依托单位:
Targeted-and Image-Based Adenovirus Cancer Therapeutic Vectors
-
批准号:8699507
-
项目类别:
-
资助金额:$46.05万
-
财政年份:2011
-
负责人:David Terry Curiel
-
依托单位:
海外基金