Develop combinatorial non-viral and viral CRISPR delivery for lung diseases
开发针对肺部疾病的组合非病毒和病毒 CRISPR 递送
基本信息
- 批准号:10274832
- 负责人:
- 金额:$ 127.79万
- 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:2018-09-10 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAnimal ModelBar CodesBasic ScienceBiotechnologyCRISPR therapeuticsCRISPR/Cas technologyCapsidCellsClustered Regularly Interspaced Short Palindromic RepeatsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNADNA SequenceDelta F508 mutationDependovirusDevelopmentDiseaseDoseEpithelial CellsEvaluationFutureGene DeliveryGene MutationGenerationsGenesGeneticGenetic DiseasesGoalsGuide RNALengthLibrariesLiverLungLung diseasesMacacaMacaca mulattaMeasuresMediatingMessenger RNAModelingMusMutationNatureNebulizerNonhomologous DNA End JoiningNonsense MutationPan GenusPharmaceutical PreparationsPhasePolymersPrimatesProductionReporterRhesusRiskSafetySerotypingSpecificityStructureSystemTechnologyTestingTherapeutic Human ExperimentationTherapeutic StudiesToxic effectVariantViralViral GenomeWorkYinairway epitheliumarmcell typecombinatorialdeep sequencingdesigngene correctiongene therapygenome editinghigh throughput screeninghomologous recombinationimprovedin vivoin vivo Modelinnovationinsertion/deletion mutationlung repairnanoparticlenanoparticle deliverynonhuman primatenovelnucleaseprotein expressionrepairedscale upsomatic cell gene editingstem cellstargeted deliverytherapeutic genome editingtherapeutic proteintool
项目摘要
Project Summary
The ability to correct disease gene mutations in vivo has broad potential utility for both therapy
and basic research. CRISPR/Cas9 is a powerful RNA-guided tool for genome editing. Our
recent discovery that CRISPR/Cas9 delivery can cure genetic disease in adult mouse liver
provided proof-of-concept of gene correction therapy in vivo. The main goal of this proposal is to
establish innovative delivery technologies to maximize the efficiency of CRISPR delivery and
gene correction in disease-relevant lung cell types. The impact of this project is a novel
paradigm of lung-targeted delivery tools for CRISPR-mediated gene correction. The
development of safe and effective delivery vehicles and genome editing tools will guide future
studies for CRISPR-mediated gene therapy. This project has three aims that focus on different
aspects of lung-directed somatic genome editing: Aim 1: Optimize NP+AAV combination for
delivery and gene correction in mouse lung; Aim 2: Identify the best AAV capsid for lung
delivery and optimize AAV genome as donor template for HDR; Aim 3: Characterize NP+AAV
developed in the UG3 phase in macaque models. This project will develop innovative designs of
adeno-associated virus and nanoparticles to significantly improve the efficiency, cell specificity,
and safety of CRISPR delivery in vivo.
项目摘要
体内纠正疾病基因突变的能力对于这两种疗法都具有广泛的潜在用途
和基础研究。CRISPR/Cas9是一种强大的RNA指导的基因组编辑工具。我们
最近发现CRISPR/Cas9递送可以治愈成年小鼠肝脏中的遗传疾病
提供了体内基因校正疗法的概念验证。该提案的主要目标是
建立创新的交付技术,以最大限度地提高CRISPR交付的效率,
疾病相关肺细胞类型的基因校正。这个项目的影响是一部小说
肺靶向递送工具的范例,用于CRISPR介导的基因校正。的
开发安全有效的运载工具和基因组编辑工具将指导未来
CRISPR介导的基因治疗研究。该项目有三个目标,侧重于不同的
目的1:优化NP+AAV组合,用于肺定向体细胞基因组编辑。
目的2:鉴定用于肺的最佳AAV衣壳
递送和优化AAV基因组作为HDR的供体模板;目标3:表征NP+AAV
在猕猴模型中的UG 3阶段开发。该项目将开发创新设计,
腺相关病毒和纳米颗粒显著提高效率,细胞特异性,
和CRISPR体内递送的安全性。
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(1)
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DANIEL G ANDERSON其他文献
DANIEL G ANDERSON的其他文献
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{{ truncateString('DANIEL G ANDERSON', 18)}}的其他基金
Nonviral delivery techniques for in vivo prime editing
用于体内引物编辑的非病毒传递技术
- 批准号:
10548169 - 财政年份:2022
- 资助金额:
$ 127.79万 - 项目类别:
Nonviral delivery techniques for in vivo prime editing
用于体内引物编辑的非病毒传递技术
- 批准号:
10344605 - 财政年份:2022
- 资助金额:
$ 127.79万 - 项目类别:
SMART BIOELECTRONIC IMPLANTS FOR CONTROLLED DELIVERY OF THERAPEUTIC PROTEINS IN VIVO AND ITS APPLICATION IN LONG-TERM TREATMENT OF HEMOPHILIA A
用于体内治疗性蛋白质控制输送的智能生物电子植入物及其在血友病 A 长期治疗中的应用
- 批准号:
10446179 - 财政年份:2022
- 资助金额:
$ 127.79万 - 项目类别:
SMART BIOELECTRONIC IMPLANTS FOR CONTROLLED DELIVERY OF THERAPEUTIC PROTEINS IN VIVO AND ITS APPLICATION IN LONG-TERM TREATMENT OF HEMOPHILIA A
用于体内治疗性蛋白质控制输送的智能生物电子植入物及其在血友病 A 长期治疗中的应用
- 批准号:
10615840 - 财政年份:2022
- 资助金额:
$ 127.79万 - 项目类别:
Combinatorial and computational design of bnAb mRNA vaccines for HIV
HIV bnAb mRNA 疫苗的组合和计算设计
- 批准号:
10592273 - 财政年份:2021
- 资助金额:
$ 127.79万 - 项目类别:
Combinatorial and computational design of bnAb mRNA vaccines for HIV
HIV bnAb mRNA 疫苗的组合和计算设计
- 批准号:
10386924 - 财政年份:2021
- 资助金额:
$ 127.79万 - 项目类别:
Interfering with the macrophage life cycle of atherosclerosis
干扰动脉粥样硬化的巨噬细胞生命周期
- 批准号:
9412185 - 财政年份:2017
- 资助金额:
$ 127.79万 - 项目类别:
High throughput microfluidic intracellular delivery platform
高通量微流控细胞内递送平台
- 批准号:
8706186 - 财政年份:2013
- 资助金额:
$ 127.79万 - 项目类别:
High throughput microfluidic intracellular delivery platform
高通量微流控细胞内递送平台
- 批准号:
8504309 - 财政年份:2013
- 资助金额:
$ 127.79万 - 项目类别:
High throughput microfluidic intracellular delivery platform
高通量微流控细胞内递送平台
- 批准号:
8839787 - 财政年份:2013
- 资助金额:
$ 127.79万 - 项目类别:
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