Ontology highlight
ABSTRACT:
PROVIDER: PRJNA842650 | ENA |
REPOSITORIES: ENA
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Project description:Genetically-engineered immune cell therapies have been in development for decades and recently have proven effective to treat some types of cancer. CRISPR-based genome editing methods enabling more flexible and targeted sequence integrations than viral transduction have potential to extend the clinical utility of cell therapies. Realization of this potential depends on improved knowledge of how coding and non-coding sites throughout the genome can be modified efficiently and on improved methods to discover novel synthetic DNA sequences that can be introduced at targeted sites to enhance critical immune cell functions. Here, we developed improved rules for non-viral genome targeting in human T cells and a pooled discovery platform to identify synthetic genome modifications that enhance therapeutically-relevant cell functions. We elucidated the breadth of targetable genomic loci by performing large knockins at 91 different genomic sites in primary human T cells, and demonstrated the power of flexible genome targeting by generating cells with Genetically Engineered Endogenous Proteins (GEEPs) that seamlessly integrate synthetic and endogenous genetic elements to alter signaling input, output, or regulatory control of genes encoding key immune receptors. Motivated by success in introducing synthetic circuits into endogenous sites, we then developed a platform to facilitate discovery of novel multi-gene circuits that reprogram both T cell specificity and function. We knocked-in barcoded pools of large DNA sequences encoding poly-cistronic gene programs. High-throughput pooled screening of targeted knock-ins to the endogenous T cell receptor (TCR) locus revealed a transcriptional regulator and novel protein chimeras that combined with a new TCR specificity to enhance T cell responses in the presence of suppressive conditions in vitro and in vivo. Overall, these pre-clinical studies provide flexible tools to discover complex synthetic gene programs that can be written into targeted genome sites to generate more effective therapeutic cells.
2021-04-19 | GSE130089 | GEO
Project description:Subgroup J avian leukemia is a type of oncology infectious disease caused by Subtype J of avian leukosis virus (ALV-J). It mainly encroaches on bone marrow cells, and metastasizes to liver, kidney, splenic ellipsoids and other organs, leading to myeloid leukosis (ML) and other malignancies, resulting in significant economic losses. microRNA play important roles in oncology infectious diseases. We used miRNA microarray analysis to detail the relationship of aberrant microRNAs and chicken ALV-J leukemia, and to try to find the potential diagnostic and therapeutic target for infections of subtype J of leukemia.
2014-03-10 | GSE28434 | GEO
Project description:Diagnosis of infectious diseases by sequencing
| PRJDB7111 | ENA
Project description:Transcriptional profiling of chicken embryo lung cells infected infectious laryngotracheitis virus (ILTV) comparing control uninfected lung cells. Goal was to determine the changes of host gene expression by ILTV infection and host-virus interaction.
2010-03-11 | GSE20630 | GEO
Project description:Data from the IAH/VLA diagnostic pathogen/virus detection microarray. The array platform for this data is GEO accession GPL5725 (provisional), and consists of 5824 oligos representing over 100 viral families, species and subtypes. The data set itself consists of 12 arrays, 4 hybridised with RNA from cell cultured foot-and-mouth disease virus (FMDV) type O, 3 hybridised with RNA from FMDV type A, 1 hybridised with RNA from a sheep infected with FMDV type O, and 4 hybridised with cell-cultured Avian Infectious Bronchitis virus (IBV). Keywords: Virus Detection Microarray
2007-08-14 | GSE8746 | GEO