DNA double-strand breaks (DSBs) are caused by either endogenous agents or exogenous ionizing radiation and chemicals. Incorrect DSB repair can lead to undesired genome rearrangements. Homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways are two major DNA repair pathways that repair DSBs and maintain genome integrity. When homologous DNA is...
The apolipoprotein E (APOE) E4 isoform is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). While APOE is predominantly expressed by astrocytes in the central nervous system, neuronal expression of APOE is of increasing interest in age-related cognitive impairment, neurological injury, and neurodegeneration. Here we show that endogenous...
Over the past fifty years, techniques for synthesizing and manipulating matter on the 1-100 nanometer scale have led to the development of nanoparticle-based approaches to both disease diagnosis and treatment. The modification of nanoparticles with biological macromolecules such as proteins and nucleic acids has led to the development of highly...
Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated Cas proteins provide an immune-like response in many prokaryotes against extraneous nucleic acids. CRISPR-Cas systems are classified into different classes and types that vary widely in composition, target recognition, and overall mechanism. The main division of CRISPR-Cas systems occurs between...
Heart failure is a growing clinical problem, and inherited cardiomyopathies contribute significantly to heart failure. Among the many genes associated with inherited cardiomyopathies, mutations in FLNC, the gene encoding the cytoskeletal protein filamin C, associate with a range of cardiomyopathy and increased risk for arrhythmia and sudden cardiac death in...
The bacterial CRISPR/Cas9 system shows promise as a genome-editing tool to treat human disease. It is integral to understand the binding and unbinding kinetics of Cas9 to its target DNA to study specificity of the Cas9 protein. Standard practices involve the use of negatively charged polymer Heparin to reduce unspecific...