While CAR therapy has begun to demonstrate efficacy, cell-engineering techniques that result in permanent genomic modification carry several safety concerns. CAR expression driven by RNA creates a platform for delivery of highly-active cell therapy while avoiding long-term CAR-driven toxicity. Using models of pediatric neuroblastoma, we have found that RNA CAR T cell activity is limited by inef...

Several recent papers show that differences in histone modification and the use of histone variants at the 5' and 3' ends of genes influence the location and kinetics of transcriptional initiation. The ultimate target of most epigenetic mechanisms may be the regulation of nucleosome occupancy, which in turn controls access to DNA at specific genomic locations.

A point mutation (E115K) resulting in slower growth of Escherichia coli DH5alpha and XL1-Blue in minimal media was identified in the purB gene, coding for adenylosuccinate lyase (ASL), through complementation with an E. coli K-12 genomic library and serial subcultures. Chromosomal modification reversing the mutation to the wild type restored growth phenotypes in minimal media.

BACKGROUND Helicobacter pylori is well known for its relationship with the occurrence of several severe gastric diseases. The mechanisms of pathogenesis triggered by H. pylori are less well known. In this study, we report the genome sequence and genomic characterizations of H. pylori strain HLJ039 that was isolated from a patient with gastric cancer in the Chinese province of Heilongjiang, wher...

The histone modification state of genomic regions is hypothesized to reflect the regulatory activity of the underlying genomic DNA. Based on this hypothesis, the ENCODE Project Consortium measured the status of multiple histone modifications across the genome in several cell types and used these data to segment the genome into regions with different predicted regulatory activities. We measured ...

Homologous Replacement is used to modify specific gene sequences of chromosomal DNA in a process referred to as "Small Fragment Homologous Replacement", where DNA fragments replace genomic target resulting in specific sequence changes. To optimize the efficiency of this process, we developed a reporter based assay system where the replacement frequency is quantified by cytofluorimetric analysis...

the aim of this study was to determine the effect of marker density, level of heritability, number of qtls, and size of training set on the genomic accuracy over three generations. thereby, a trait was simulated with heritability of 0.10, 0.25 or 0.40. for each animal, a genome with 20 chromosomes, 1 morgan each, was simulated. different marker densities (2000, 4000 and 6000 markers) and 400 an...

Gene targeting by single-stranded oligodeoxyribonucleotides (ssODNs) is a promising tool for site-specific gene modification in mouse embryonic stem cells (ESCs). We have developed an ESC line carrying a mutant EGFP reporter gene to monitor gene correction events shortly after exposure to ssODNs. We used this system to compare the appearance and fate of cells corrected by sense or anti-sense ss...

The term epigenetic modification denotes reversible traits of gene expression that do not include alterations to the DNA sequence. These epigenetic alterations are responsible for chromatin structure stability, genome integrity, modulation of tissue-specific gene expression, embryonic development, genomic imprinting and X-chromosome inactivation in females. Epigenetic changes include reversible...

Mycoplasma pulmonis possesses a cassette of genes that are predicted to code for type III restriction and modification (R-M) enzymes. Transposon disruption of a gene predicted to code for the endonuclease subunit of the enzyme resulted in loss of R-M activity. Genomic data indicate that the cassette was acquired by horizontal gene transfer and possibly located on a mobile element.