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Challenges in Delivering Gene Therapy
Published in Yashwant Pathak, Gene Delivery, 2022
Lastly, another strategy to circumvent an immune response while using gene therapy is the modifications to the promoter to drive transgene expression. When specific promoters are used for gene therapy, the expression level of certain genes vary depending on the promoter used. Regulated promoters in inflammatory conditions can usually lead to an effective approach for circumventing immune responses and gene therapy. Researchers have found that the murine acute phase protein can express under inflammatory conditions and avoid transient expression of targeted gene induction [46].
Operations on Genomic Intervals and Genome Arithmetic
Published in Altuna Akalin, Computational Genomics with R, 2020
Following from the exercise above, get the promoters of Refseq transcripts (-1000bp and +1000 bp of the TSS) and calculate what percentage of them overlap with CpG islands. HINT: You have to get the promoter coordinates and use the findOverlaps() or subsetByOverlaps() from the GenomicRanges package. To get promoters, type ?promoters on the R console and see how to use that function to get promoters or calculate their coordinates as shown in the chapter. [Difficulty: Beginner/Intermediate]
Genetic Manipulation of Human Marrow: Gene Transfer Using Retroviruses
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
Philip Hughes, R. Keith Humphries
Alternatively, one can choose a promoter in order to enhance the expression of the gene without specificity; that is, use an ubiquitously expressed promoter, such as the thymidine kinase promoter or a promoter from another virus such as cytomegalovirus.20 The use of an internal, highly active promoter attempts to provide prolonged, enhanced expression without the downregulation that may befall LTR-promoted genes. However, internal promoters that have produced high expression when tested in cell lines, do not necessarily do the same in hematopoietic progenitor cells or more primitive cells.18,21 One difficulty with adding internal promoters, enhancers, or additional sequences is that the vectors become more complex, and the chance of genetic rearrangement increases, either within the viral-producing cell line or within the target cell, leading to potentially decreased or aberrant expression.
Genome-wide DNA methylation profiles analysis in primary warm autoimmune hemolytic anemia patients
Published in Hematology, 2023
Manjun Zhao, Yang Zhang, Jin Yang, Lei Chen, Ziying Zhang, Huaquan Wang, Zonghong Shao, Limin Xing
In this study, we found that total DNA methylation levels of both C and CG type bases in the patient with AIHA were lower than those in the HC. In the patient with AIHA, DNA methylation levels of C bases and CG type bases in regions of the whole genome regulatory element, such as coding sequence, up2Kb, down2Kb, and mRNA regions, were lower than those in the HC. These data preliminarily demonstrate that DNA methylation profiles differ between patients with AIHA and HC. A total of 30,180 DMRs were identified on 23 chromosomes of the patient with AIHA. There are two types of corresponding relationships between DMRs and their downstream genes. First, any regions identified as DMRs can be screened into the Gene List as DMR-related genes. Second, only promoters identified as DMRs can be screened into the Gene List as genes corresponding to DMR-related promoters. Studies have found that the pathways enriched by the KEGG public database for downstream genes screened by two different corresponding relationships overlap. Phospholipase D (PLD), HIF-1, Rap1, and Ras signaling pathways were enriched in two different analyses. Many studies have found that abnormal activation of these signaling pathways is correlated with the occurrence of multiple AIDs.
Detection of endocrine and metabolism disrupting xenobiotics in milk-derived fat samples by fluorescent protein-tagged nuclear receptors and live cell imaging
Published in Toxicology Mechanisms and Methods, 2023
Keshav Thakur, Emmagouni Sharath Kumar Goud, Yashika Jawa, Chetan Keswani, Suneel Onteru, Dheer Singh, Surya P. Singh, Partha Roy, Rakesh K. Tyagi
Cell-based promoter-reporter assays have also been commonly used for diverse NRs to assess the action of small molecule modulators. Detection of ligands that activate the NR transcription function is relatively easy to study. However, ligands that bind NRs as pure antagonists are difficult to detect directly and require additional assays (Tyagi et al. 2000). Nuclear translocation of cytoplasmic NRs (like AR and ERα) is a unidirectional joint action of agonists and antagonists in a mixture. They do not impede each other’s actions contrary to what is observed in promoter-reporter-based transcription assays. In this context, a mixture of agonists and antagonists together will translocate the receptor, mostly additively which works favorably in such assay designs. Therefore, this prototype cell-based assay opens abundant options and opportunities to evaluate the safety of milk, utilizing the NR platform. Interestingly, the simplicity, novelty, and cost-effectiveness associated with this assay are also additional advantages.
Association between the Genetic Polymorphisms of CCL2, CCL5, CCL8, CCR2, and CCR5 with Chronic Hepatitis C Virus Infection in the Chinese Han Population
Published in Immunological Investigations, 2022
Lin-Nan Shao, Shi-Hang Zhou, Ni Wang, Shu-Ting Zhang, Ming Liu
Transcriptional factors regulate gene expression by binding to the promoter region (Sun et al. 2017). To further clarify the association between rs1024610 polymorphism in the CCL2 promoter region and CCL2 production, we performed transient transfection studies. In dual-luciferase reporter assays, the luciferase activity associated with the rs1024610 allele T construct was higher than that associated with the A allele construct, although this difference was not statistically significant (P = .072). This finding is consistent with our previous results showing that rs1024610 does not influence plasma levels of CCL2. Nevertheless, prediction of potential transcription factors using the online software, JASPAR (http://jaspar.genereg.net/), revealed that when the A allele was converted to T, the number of potential binding transcription factors increased from VENTX alone to VENTX and PAX3. Thus, we conjectured that the difference in luciferase activity may be more significant if HEK293 cells were stimulated by some ligands; however, further research is required to confirm this hypothesis.