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Reprogramming iPS Cells with Exogenous and Endogenous Transcription Factor Genes

使用外源和内源转录因子基因重编程 iPS 细胞

基本信息

批准号：
8917047
负责人：
YUET Wai KAN
金额：
$ 38.14万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8917047
关键词：
Adenovirus Vector Amniotic Fluid Bacterial Chromosomes Bacteriophages Biopsy Cell Culture Techniques Cell Therapy Cell physiology Cells Chemicals Chorionic Villi Sampling Chromosomes Complementary DNA Coupled Development Diagnosis Dimensions Disease Double-Stranded RNA Early treatment Ensure Enzymes Epigenetic Process FLT4 gene Fibroblasts Future Gene Expression Generations Genes Genetic Recombination Genome Hematopoietic Hemoglobinopathies Hereditary Disease Homologous Gene Human Human Genome Instruction Integrase Legal patent Lentivirus Vector Link Location Mediating Methods Mus Patients Peptides Plasmid Cloning Vector Plasmids Prenatal Diagnosis Procedures Property Proteins RNA RNA Interference Reporting Research Personnel Retroviral Vector Sarna Sequence Homologs Sickle Cell Anemia Site Skin Small Interfering RNA Somatic Cell Stem cells System Techniques Tetracyclines Thalassemia Time Transcription factor genes Transgenes Virus base beta Thalassemia c-myc Genes cell type combinatorial gene function high throughput screening human disease improved induced pluripotent stem cell innovation integration site mammalian genome mouse genome novel programs promoter site-specific integration small molecule stem transcription factor vector

项目摘要

PROJECT SUMMARY (See Instructions): Proj 1: The discovery of reprogramming somatic cells to induced pluripotent stem cells has opened new dimensions for the study and treatment of human diseases. Since the first description of reprogramming mouse IPS cells by introducing 4 transcription factor genes with retroviral vectors, mouse and human cells of many cell types have been successfully reprogrammed. Although retroviral vectors are still the most proficient vehicles for reprogramming, their property of random integration may cause damage by disrupting vital host gene functions. Many other vehicles for introducing transcription factors have been reported, including plasmids, EB based plasmid vectors, adenoviral vectors, transposons, lentiviral vectors and proteins. Some of these methods are inefficient for reprogramming human somatic cells. Lentiviral vectors also integrate randomly into the genome although they could be removed with cre-lox. The aim of this project is to investigate novel IPS techniques that can be applied in the future to the treatment of sickle cell disease and B-thalassemia, the 2 most common genetic diseases. We will use 2 strategies. The first is to introduce the 4 transcription factor genes 0CT4, S0X2, FLT4 and cMYC linked by 2A peptides using PhiC31 integrase fpr site-specific integration. The second strategy, directed by the co-investigator Long-Cheng Li, will use his innovation of short activator double stranded RNA to stimulate the expression ofthe endogenous transcription factor genes. He has shown that these saRNAs can stimulate expression of endogenous genes of various kinds. The strategies we propose have the advantage of not disturbing the functions of the host genes. Our project is directed to eventual application to sickle cell disease and thalassemia. We will reprogram skin biopsy cells from patents as well as amniotic fluid and CVS cells which will be useful for early cell therapy after prenatal diagnosis.

项目概述（见项目说明）：