Phase 2: NIS proteins with altered anion specificity
第 2 阶段:阴离子特异性改变的 NIS 蛋白
基本信息
- 批准号:9346708
- 负责人:
- 金额:$ 73.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-16 至 2019-03-31
- 项目状态:已结题
- 来源:
- 关键词:Adenovirus VectorAdenovirusesAlpha Particle EmitterAmino AcidsAnimalsAnionsAwardBackBiological AssayCell TherapyCellsCommunitiesCorrelative StudyDNADataDependovirusDetectionDevelopmentDiagnosticDiscipline of Nuclear MedicineDoseGene TransferGenerationsGenesGoalsGrantHalf-LifeHomologous GeneHourHumanImageImageryImmunoblottingIn VitroIodidesIsotopesLentivirus VectorLongevityMammalsMeasuresMediatingMedicalMessenger RNAModelingMonitorMusMutagenesisMutationPerchloratesPerformancePhasePopulationPositronPositron-Emission TomographyProductionProteinsQuantitative Reverse Transcriptase PCRReporterReporter GenesResistanceResolutionSLC5A5 geneSerotypingSignal TransductionSmall Business Innovation Research GrantSpecificityStructure-Activity RelationshipTechnologyTestingThyroid GlandTissue HarvestingTissuesTracerVariantVirusanimal imagingcellular transductiongene therapygene transfer vectorimmunogenicityimprovedin vivoinsightinstrumentationinterestmolecular dynamicsmutantnext generationnon-invasive imagingoptical spectraperrhenateradioiodine therapyradiotracerscreeningsingle photon emission computed tomographytooluptakevectorvector biodistribution
项目摘要
Abstract
Imanis is a reporter gene imaging company which has chosen to emphasize NIS technology over other
reporter proteins. NIS is the sodium iodide symporter, which mediates the uptake and concentration of iodide
in the thyroid gland, providing the basis for diagnostic thyroid radioimaging and radioiodine therapy. NIS
reporter gene technology allows accurate, sensitive, high-resolution visualization of NIS-modified cells, genes
and viruses in living mammals (mouse to human). Additionally, NIS lacks immunogenicity (NIS is a self-protein)
and is harmless to targeted tissues, allowing for longitudinal imaging throughout the lifespan of the animal.
NIS-expressing cells and tissues can be imaged with a variety of readily available anionic radiotracers such as
125I, 124I, 125I, B18F4 (tetraflouoroborate) and 99mTcO4 (pertechnetate) NIS-expressing cells can also be destroyed
using beta- or alpha- particle emitting anions (131I, 188ReO4/perrhenate, or 211Astatide). The overarching goal of
this SBIR application is to generate NIS variants that can be used to enhance the sensitivity of NIS reporter
gene imaging to monitor virus, gene and cell therapies. During Phase I part of the award, we screened a large
number of NIS mutations. We have subsequently identified and generated NIS mutants that demonstrated
superior isotope uptake and met the agreed milestone of the Phase I grant. In this Phase II application, we will
build on those findings and will develop, validate and market the next generation of NIS reporter genes tailored
specifically for optimal performance with 99mTcO4 and B18F4 radiotracers. These NIS variants will be
commercially developed to provide the scientific and medical community with vastly improved in vivo reporter
gene imaging solutions.
摘要
Imanis是一家记者基因成像公司,该公司选择强调NIS技术而不是其他技术
报告蛋白。NIS是钠碘同向转运体,介导碘的摄取和浓缩
在甲状腺中,为诊断性甲状腺放射成像和放射性碘治疗提供了基础。NIS
报告基因技术允许准确、灵敏、高分辨率地观察NIS修饰的细胞、基因、
以及活的哺乳动物(从小鼠到人类)中的病毒。此外,NIS缺乏免疫原性(NIS是一种自身蛋白)
并且对目标组织无害,允许在动物的整个寿命期间进行纵向成像。
表达NIS的细胞和组织可以用多种容易获得的阴离子放射性示踪剂成像,
~(125)I、~(124)I、~(125)I、B18 F4(四氟硼酸盐)和~(99)mTcO_4(高锝酸盐)NIS表达细胞也可被破坏
使用β-或α-粒子发射阴离子(131 I、188 ReO 4/过碘酸盐或211 Astatide)。的首要目标
该SBIR应用程序用于生成可用于增强NIS报告基因灵敏度的NIS变体
基因成像用于监测病毒、基因和细胞疗法。在颁奖的第一阶段,我们筛选了大量
NIS突变的数量。我们随后鉴定并产生了NIS突变体,
上级同位素吸收,并达到了第一阶段赠款的商定里程碑。在第二阶段的申请中,我们将
在这些发现的基础上,开发、验证和销售下一代NIS报告基因
专门用于99 mTcO 4和B18 F4放射性示踪剂的最佳性能。这些NIS变体将
商业开发,为科学和医学界提供大大改进的体内报告
基因成像解决方案。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
KAH-WHYE PENG其他文献
KAH-WHYE PENG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('KAH-WHYE PENG', 18)}}的其他基金
Intravenous Administration of Vesicular Stomatitis Vectors
水泡性口炎载体的静脉注射
- 批准号:
8875637 - 财政年份:2014
- 资助金额:
$ 73.15万 - 项目类别:
Intravenous Administration of Vesicular Stomatitis Vectors
水泡性口炎载体的静脉注射
- 批准号:
8643433 - 财政年份:2014
- 资助金额:
$ 73.15万 - 项目类别:
Intravenous Administration of Vesicular Stomatitis Vectors
水泡性口炎载体的静脉注射
- 批准号:
9281688 - 财政年份:2014
- 资助金额:
$ 73.15万 - 项目类别:
Intravenous Administration of Vesicular Stomatitis Vectors
水泡性口炎载体的静脉注射
- 批准号:
9071379 - 财政年份:2014
- 资助金额:
$ 73.15万 - 项目类别:
Intravenous Administration of Vesicular Stomatitis Vectors
水泡性口炎载体的静脉注射
- 批准号:
9040540 - 财政年份:2014
- 资助金额:
$ 73.15万 - 项目类别:
Enhancing localization of therapeutic viruses and cells to tumor sites
增强治疗性病毒和细胞对肿瘤部位的定位
- 批准号:
8403539 - 财政年份:2009
- 资助金额:
$ 73.15万 - 项目类别:
Enhancing localization of therapeutic viruses and cells to tumor sites
增强治疗性病毒和细胞对肿瘤部位的定位
- 批准号:
8005518 - 财政年份:2009
- 资助金额:
$ 73.15万 - 项目类别:
Enhancing localization of therapeutic viruses and cells to tumor sites
增强治疗性病毒和细胞对肿瘤部位的定位
- 批准号:
8211042 - 财政年份:2009
- 资助金额:
$ 73.15万 - 项目类别:
Enhancing localization of therapeutic viruses and cells to tumor sites
增强治疗性病毒和细胞对肿瘤部位的定位
- 批准号:
8600868 - 财政年份:2009
- 资助金额:
$ 73.15万 - 项目类别:
Enhancing localization of therapeutic viruses and cells to tumor sites
增强治疗性病毒和细胞对肿瘤部位的定位
- 批准号:
7760838 - 财政年份:2009
- 资助金额:
$ 73.15万 - 项目类别:
相似海外基金
cGAS-STING Pathway Targeting Replicative Adenoviruses with CD46 Tropism and AFP Promoter Conditional Replication Restriction for the Treatment of Hepatocellular Carcinoma
cGAS-STING 通路靶向具有 CD46 趋向性和 AFP 启动子的复制腺病毒条件性复制限制用于治疗肝细胞癌
- 批准号:
10436626 - 财政年份:2021
- 资助金额:
$ 73.15万 - 项目类别:
Glioma therapy with oncolytic adenoviruses and immunometabolic adjuvants
溶瘤腺病毒和免疫代谢佐剂治疗胶质瘤
- 批准号:
10557162 - 财政年份:2021
- 资助金额:
$ 73.15万 - 项目类别:
Molecular therapy of replication-competent adenoviruses targeting characteristic gene mutations found in mesothelioma
针对间皮瘤中发现的特征基因突变的具有复制能力的腺病毒的分子疗法
- 批准号:
21K08199 - 财政年份:2021
- 资助金额:
$ 73.15万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Glioma therapy with oncolytic adenoviruses and immunometabolic adjuvants
溶瘤腺病毒和免疫代谢佐剂治疗胶质瘤
- 批准号:
10330464 - 财政年份:2021
- 资助金额:
$ 73.15万 - 项目类别:
Structural characterization of nucleoprotein cores of human adenoviruses
人腺病毒核蛋白核心的结构表征
- 批准号:
9807741 - 财政年份:2019
- 资助金额:
$ 73.15万 - 项目类别:
Molecular biology and pathogenesis of fowl adenoviruses
禽腺病毒的分子生物学和发病机制
- 批准号:
41625-2013 - 财政年份:2018
- 资助金额:
$ 73.15万 - 项目类别:
Discovery Grants Program - Individual
The therapeutic strategies with augmented replications of oncolytic adenoviruses for malignant mesothelioma
溶瘤腺病毒增强复制治疗恶性间皮瘤的治疗策略
- 批准号:
18K15937 - 财政年份:2018
- 资助金额:
$ 73.15万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Molecular biology and pathogenesis of fowl adenoviruses
禽腺病毒的分子生物学和发病机制
- 批准号:
41625-2013 - 财政年份:2017
- 资助金额:
$ 73.15万 - 项目类别:
Discovery Grants Program - Individual
Exploring the effects of nutrient deprivation on T cells and oncolytic adenoviruses, in order to create immune activators for tumour therapy
探索营养剥夺对 T 细胞和溶瘤腺病毒的影响,以创造用于肿瘤治疗的免疫激活剂
- 批准号:
1813152 - 财政年份:2016
- 资助金额:
$ 73.15万 - 项目类别:
Studentship
Research on detection of novel adenoviruses by genetic methods
新型腺病毒的基因检测研究
- 批准号:
16K09118 - 财政年份:2016
- 资助金额:
$ 73.15万 - 项目类别:
Grant-in-Aid for Scientific Research (C)