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Molecular tools for targeting RNA

用于靶向 RNA 的分子工具

基本信息

批准号：
10242950
负责人：
Patrick Hsu
金额：
$ 33.63万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10242950
关键词：
Adopted Alternative Splicing Amino Acids Binding Biochemical Bioinformatics Biological Models Biomedical Research CRISPR/Cas technology Catalogs Cell physiology Cells Clustered Regularly Interspaced Short Palindromic Repeats Code Communities Complement DNA DNA Binding Domain Deoxyribonucleases Dependovirus Development Diagnostic Disease Elements Engineering Enzymes Foundations Frontotemporal Dementia Future Gene Expression Genes Genetic Diseases Genetic Transcription Genetic Variation Genetic study Genome Genome engineering Genomics Goals Guide RNA Human Image Individual Knock-in Light Mainstreaming Mammalian Cell Maps Modeling Molecular Neurons Nucleic Acids Nucleotides Pancreatic ribonuclease Patients Phenotype Protein Engineering Protein Isoforms RNA RNA Binding RNA Interference RNA Splicing Regulation Research Ribonucleases Scientist Site Small RNA Structure System Tau isoform ratio Technology Therapeutic Transcript Untranslated RNA Variant Viral Viral Vector Work adeno-associated viral vector base epigenome editing expression vector flexibility genome editing genomic locus induced pluripotent stem cell interest knock-down knockout gene next generation sequencing novel nuclease optogenetics programs public health relevance spatiotemporal stem cell differentiation therapeutic development tool transcriptome transcriptome sequencing vector

项目摘要

Abstract Due to rapid advances in RNA sequencing, scientists now have the ability to easily map transcriptome changes in cellular function and disease to complement a robust catalog of functional genome elements and variants. Genome editing tools, in particular the CRISPR-Cas9 platform, allow for rapid control and manipulation of genome sequences for genetic study. To extend these tools to the direct and facile perturbation of RNA, the proposed work aims to develop a broad suite of transcriptome engineering tools based on diverse RNA-targeting CRISPR systems to complement RNAi. Analogous to dCas9 for DNA, programmable RNA binding will enable modular modes of function including and beyond RNA knockdown, such as splice isoform engineering, by leveraging a combination of bioinformatic, biochemical, and protein engineering approaches to demonstrate and optimize the utility of the system. Using patient-derived induced pluripotent stem cells differentiated into neurons as a model system, RNA mis-splicing diseases will be targeted as a proof-of-concept to modulate alternative splicing. This proposal expects to enable a robust, flexible platform to interrogate gene expression, study transcript dynamics, and dissect the function of coding and noncoding transcripts.

摘要