Rhodopsin Gene Correction and Gene Knockout in Rod Cells
视杆细胞中的视紫红质基因校正和基因敲除
基本信息
- 批准号:7686532
- 负责人:
- 金额:$ 4.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-03-01 至 2011-02-28
- 项目状态:已结题
- 来源:
- 关键词:AnimalsBiological AssayCell physiologyCellsCleaved cellCountDNADNA DamageDefectDependovirusDetectionDiseaseDouble Strand Break RepairEffectivenessEventExonsEye diseasesFluorescenceFoundationsFrequenciesGene ExpressionGenesGenomeGenomicsGoalsGrantGreen Fluorescent ProteinsHumanIndividualIntronsKnock-in MouseKnock-outLeadLocalizedMeasuresMessenger RNAMetabolismMethodsMusMutateMutationNeurodegenerative DisordersNeuronsNonsense-Mediated DecayOcular PhysiologyPhotoreceptorsPoisonProceduresProcessPropertyProteinsRangeReagentResearch PersonnelRetinaRetinal DegenerationRetinitis PigmentosaRhodopsinRod Outer SegmentsSiteStructureSystemTestingTherapeuticZinc Fingersadeno-associated viral vectorbasedesignfusion genegene correctiongene repairgenetic manipulationhomologous recombinationknockout genemouse genomemutantnovelnucleaseprogramsrepairedresearch studyretinal rodssubretinal injectiontherapy design
项目摘要
Strategies for correction and knockout of the rhodopsin gene in rod photoreceptor cells will be tested to
determine what it takes to manipulate the structure and expression of deleterious genes in terminally
differentiated neurons. We seek to understand the fundamental cellular processes that allow targeted gene
repair and mutation in these cells, as well as those that can control expression of toxic proteins. In the process
of gaining this understanding, we aim to develop effective methods for treating autosomal dominant retinitis
pigmentosa (ADRP) caused by defects in the rhodopsin gene. Successful therapies for ADRP will provide a
paradigm for treatment of dominant eye diseases and other neurodegenerative disorders. Mice are a natural
choice for these studies because their eye physiology resembles that of humans;ADRP disease genes cause
retinal degeneration in mice more quickly than in humans and large animals, allowing rapid testing of
efficacy; and mouse genomes can be readily manipulated. Previously, we fused the complete human
rhodopsin gene¿the ultimate target for therapy¿tothe GFP gene to generate a visible marker for rhodopsin
expression that localizes properly to rod outer segments. Here, we propose to use our existing wild type
rhodopsin-GTP mice and generate four new mouse lines carrying mutant human rhodopsin-GFP genes to
provide targets for various kinds of genetic manipulation. These modified human rhodopsin-GFP genes will
include three defined ADRP mutations¿P23H, Q64ter, and Q344ter¿and a gene that carries an internal
duplication. Adeno-associated virus vectors will be used to deliver novel reagents for rhodopsin correction
and knockout. For gene correction, we will test segments of rhodopsin DNA in the presence and absence of
genes for zinc-finger nucleases (ZFNs) that have been rationally designedto cleave near the target mutations.
For gene knockout, we will test exon-specific ZFNs to mutate the rhodopsin-GFP gene directly, and intron-
specific ZFNs designed to stimulate incorporation of a 'killer' exon that will poison expression of the
rhodopsin gene. Assays for rhodopsin gene correction and knockout will utilize the fluorescent properties of
the humanrhodopsin-GFPtarget gene.
校正和敲除视杆光感受器细胞中视紫红质基因的策略将被测试
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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JOHN H WILSON其他文献
JOHN H WILSON的其他文献
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{{ truncateString('JOHN H WILSON', 18)}}的其他基金
Instability of Triplet Repeats in Mammalian Cells
哺乳动物细胞中三联体重复的不稳定性
- 批准号:
7904472 - 财政年份:2009
- 资助金额:
$ 4.94万 - 项目类别:
Rhodopsin Gene Correction and Gene Knockout in Rod Cells
视杆细胞中的视紫红质基因校正和基因敲除
- 批准号:
8655854 - 财政年份:1997
- 资助金额:
$ 4.94万 - 项目类别:
RHODOSPIN GENE CORRECTION BY OLIGONUCLEOTIDE TARGETING
通过寡核苷酸靶向进行视紫红质基因校正
- 批准号:
6314816 - 财政年份:1997
- 资助金额:
$ 4.94万 - 项目类别:
Rhodopsin Gene Correction and Gene Knockout in Rod Cells
视杆细胞中的视紫红质基因校正和基因敲除
- 批准号:
7186678 - 财政年份:1997
- 资助金额:
$ 4.94万 - 项目类别:
Rhodopsin Gene Correction and Gene Knockout in Rod Cells
视杆细胞中的视紫红质基因校正和基因敲除
- 批准号:
7386597 - 财政年份:1997
- 资助金额:
$ 4.94万 - 项目类别:
RHODOPSIN GENE CORRECTION BY OLIGONUCLEOTIDE TARGETING
通过寡核苷酸靶向进行视紫红质基因校正
- 批准号:
2020240 - 财政年份:1997
- 资助金额:
$ 4.94万 - 项目类别:
RHODOSPIN GENE CORRECTION BY OLIGONUCLEOTIDE TARGETING
通过寡核苷酸靶向进行视紫红质基因校正
- 批准号:
6041352 - 财政年份:1997
- 资助金额:
$ 4.94万 - 项目类别:
RHODOSPIN GENE CORRECTION BY OLIGONUCLEOTIDE TARGETING
通过寡核苷酸靶向进行视紫红质基因校正
- 批准号:
6635654 - 财政年份:1997
- 资助金额:
$ 4.94万 - 项目类别:
Rhodopsin Gene Correction and Gene Knockout in Rod Cells
视杆细胞中的视紫红质基因校正和基因敲除
- 批准号:
8260502 - 财政年份:1997
- 资助金额:
$ 4.94万 - 项目类别:
Rhodopsin Gene Correction and Gene Knockout in Rod Cells
视杆细胞中的视紫红质基因校正和基因敲除
- 批准号:
8117905 - 财政年份:1997
- 资助金额:
$ 4.94万 - 项目类别:
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