Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human Disease
Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human Disease
批准号:
10676734
负责人:
Brittany S. Adamson
金额:
$250.0万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
未结题
起止时间:
2017-08-08 至 2027-05-31
关键词:
3-DimensionalAccelerationArchitectureBCAR1 geneBase PairingBiochemistryBioinformaticsBiologicalBiologyCRISPR/Cas technologyCellsChemicalsClustered Regularly Interspaced Short Palindromic RepeatsCodeComplementComplexDNADNA BindingDNA Repair PathwayDNA SequenceDNA sequencingDetectionDevelopmentDiseaseEducationEducation and OutreachEndonuclease IEngineeringEnhancersEnvironmentEpigenetic ProcessEvolutionExposure toGene ExpressionGeneral HospitalsGenerationsGenesGeneticGenetic DiseasesGenetic TranscriptionGenetic VariationGenomeGenome engineeringGenomic approachGenomicsGoalsHeritabilityHumanHuman GeneticsHuman GenomeIndividualInterdisciplinary StudyMassachusettsMedicineMessenger RNAMethodsMitochondriaMitochondrial DNAMitoticMolecularMutationNeoplasm MetastasisNuclearOutputPathway interactionsPhylogenetic AnalysisPopulationPreventive MedicineProcessProtein EngineeringProteinsRecording of previous eventsRegulatory ElementRepressionResearchResearch PersonnelResolutionResourcesSafetyStructureStudentsSystemTalentsTechnologyTherapeuticTherapeutic InterventionTimeTissuesToxic effectTrainingUniversitiesUntranslated RNAVariantVirus DiseasesZinc Fingersbase editorcellular engineeringepigenomeepigenome editingexperiencefunctional genomicsgenetic variantgenome editinggenome scienceshuman diseaseimprovedin vivolife historymedical schoolsmitochondrial genomemolecular clockmultidisciplinarynext generationnovelnovel strategiesnovel therapeuticsnucleasepersonalized medicinepostmitoticprime editingprime editorresearch and developmentresearch facilityresponseskill acquisitionsocioeconomicsspatial integrationtooltraining opportunitytumor
中文摘要
基因组编辑和记录中心:项目总结
英文摘要
CENTER FOR GENOME EDITING AND RECORDING: PROJECT SUMMARY
Recent advances in DNA sequencing and bioinformatics have generated vast numbers of sequence variants
associated with disease that, in principle, hold the keys to breakthroughs in preventive medicine and
therapeutic intervention. However, realizing the promise of personalized medicine will require accurate
manipulation of DNA sequences and gene expression as well as interrogation of the functional consequences
of sequence variants at a scale and level of accuracy not currently possible.
The Center for Genome Editing and Recording (CGER) will address these challenges by creating
technologies to detect, alter and record the sequence and output of the genome in individual cells and tissues.
The CGER will exploit the programmable DNA binding and nickase activity of CRISPR-Cas proteins as well as
engineered zinc finger and TALE proteins to create a new generation of tools to precisely engineer the genome
and epigenome. These platforms will enable high-precision engineering of both the nuclear and mitochondrial
genomes as well as heritable silencing or activation of messenger RNAs, long noncoding RNA and a host of
other regulatory elements such as enhancers and insulator regions. Critically, these alterations can be made
without introducing double stranded breaks to DNA, thereby avoiding DNA toxicity and minimizing reliance on
complex and difficult-to-control endogenous DNA repair pathways. Collectively, these technologies will usher in
a new era of safer, high precision and multiplexed genome and epigenome editing.
In addition, we will exploit these platforms to develop higher-level multichannel molecular recorders that
will allow us to track and reconstruct the life history of cells in an in vivo setting. We will add the ability to follow
cells in space and time as well as record the history of their past cellular states to the existing phylogenetic
lineage tracing systems pioneered in the previous embodiment of this Center.
The center will be led by a team that collectively has a remarkable track record of developing bold,
impactful new tools to expand their precision, efficacy, safety and scope, and finally exploiting these new
capabilities to develop novel strategies to explore fundamental biological and biomedical problems. Our
multidisciplinary team has a rich history of working together, which has been greatly accelerated by the CEGS
structure in a manner that would simply not be possible if each co-PI had been working on similar problems in
isolation. Leveraging the capabilities of the Whitehead Institute, MIT, The Broad Institute, Harvard University,
Harvard Medical School, The Lewis Sigler Institute for Integrative Genomics at Princeton and the
Massachusetts General Hospital, we aim to create transformative capabilities and have access to state-of-the-
art research facilities as well as resources for training, education and outreach that will attract diverse talent to
the field of genomics research.
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DOI:
10.1242/jcs.261216
发表时间:
2023-05-15
期刊:
Journal of cell science
影响因子:
4
作者:
[]
通讯作者:
DOI:
10.1038/s41586-020-1978-5
发表时间:
2020-02
期刊:
Nature
影响因子:
64.8
作者:
[Doudna JA]
通讯作者:
Doudna JA
DOI:
10.1038/s41587-020-0609-x
发表时间:
2021-01
期刊:
Nature biotechnology
影响因子:
46.9
作者:
[Kurt IC, Zhou R, Iyer S, Garcia SP, Miller BR, Langner LM, Grünewald J, Joung JK]
通讯作者:
Joung JK
DOI:
10.1126/science.abi6983
发表时间:
2022-03-11
期刊:
SCIENCE
影响因子:
56.9
作者:
[Cho, Nathan H., Cheveralls, Keith C., Brunner, Andreas-David, Kim, Kibeom, Michaelis, Andre C., Raghavan, Preethi, Kobayashi, Hirofumi, Savy, Laura, Li, Jason Y., Canaj, Hera, Kim, James Y. S., Stewart, Edna M., Gnann, Christian, McCarthy, Frank, Cabrera, Joana P., Brunetti, Rachel M., Chhun, Bryant B., Dingle, Greg, Hein, Marco Y., Huang, Bo, Mehta, Shalin B., Weissman, Jonathan S., Gomez-Sjoberg, Rafael, Itzhak, Daniel N., Royer, Loic A., Mann, Matthias, Leonetti, Manuel D.]
通讯作者:
Leonetti, Manuel D.
DOI:
10.1038/nature24268
发表时间:
2017-10-19
期刊:
Nature
影响因子:
64.8
作者:
[Chen JS, Dagdas YS, Kleinstiver BP, Welch MM, Sousa AA, Harrington LB, Sternberg SH, Joung JK, Yildiz A, Doudna JA]
通讯作者:
Doudna JA
共 23 条
Mapping the DNA damage response in human cells with high-resolution functional genomics
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批准号:10655450
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项目类别:
-
资助金额:$39.97万
-
财政年份:2020
-
负责人:Brittany S. Adamson
-
依托单位:
Mapping the DNA damage response in human cells with high-resolution functional genomics
-
批准号:10461118
-
项目类别:
-
资助金额:$39.97万
-
财政年份:2020
-
负责人:Brittany S. Adamson
-
依托单位:
Mapping the DNA damage response in human cells with high-resolution functional genomics
-
批准号:10029232
-
项目类别:
-
资助金额:$39.97万
-
财政年份:2020
-
负责人:Brittany S. Adamson
-
依托单位:
Mapping the DNA damage response in human cells with high-resolution functional genomics
-
批准号:10245257
-
项目类别:
-
资助金额:$39.97万
-
财政年份:2020
-
负责人:Brittany S. Adamson
-
依托单位:
Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human Disease
-
批准号:10408424
-
项目类别:
-
资助金额:$250.0万
-
财政年份:2017
-
负责人:Brittany S. Adamson
-
依托单位:
海外基金