Higher Seroprevalence of Anti-Adeno-Associated Viral Vector Neutralizing Antibodies Among Racial Minorities in the United States.

Anti-adeno-associated viral vector (AAV) neutralizing antibodies (NAbs) can ablate efficacy of transgene expression following intravenous vector administration. This observation in both preclinical and clinical trials has led to exclusion of NAb-positive patients from receiving AAV gene therapy. AAV drug development includes selection of capsids with lower NAb seroprevalence that also possess other favorable traits.

Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

Background: Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients.

AAV-ID: A Rapid and Robust Assay for Batch-to-Batch Consistency Evaluation of AAV Preparations.

Adeno-associated virus (AAV) vectors are promising clinical candidates for therapeutic gene transfer, and a number of AAV-based drugs may emerge on the market over the coming years. To insure the consistency in efficacy and safety of any drug vial that reaches the patient, regulatory agencies require extensive characterization of the final product. Identity is a key characteristic of a therapeutic product, as it ensures its proper labeling and batch-to-batch consistency.

In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector.

Adeno-associated virus (AAV) vectors have emerged as a gene-delivery platform with demonstrated safety and efficacy in a handful of clinical trials for monogenic disorders. However, limitations of the current generation vectors often prevent broader application of AAV gene therapy. Efforts to engineer AAV vectors have been hampered by a limited understanding of the structure-function relationship of the complex multimeric icosahedral architecture of the particle.

A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCgamma1 activation and angiogenesis.

Activation of phospholipase Cgamma1 (PLCgamma1) by vascular endothelial growth factor receptor-2 (VEGFR-2) in endothelial cells in part is responsible for angiogenesis in vivo. The cellular mechanisms exerting negative control over PLCgamma1 activation, however, remain unaddressed. Here by using in vitro and in vivo binding assays, we show that the Casitas B-lineage lymphoma (c-Cbl) E3 ubiquitin ligase constitutively associates with PLCgamma1 via its C-terminal domain and conditionally interacts with VEGFR-2 via the N-terminal/TKB domain.

Lifelong caloric restriction increases expression of apoptosis repressor with a caspase recruitment domain (ARC) in the brain.

Aging may increase apoptotic events and the susceptibility of the central nervous system to apoptosis. Calorie restriction has been shown to have neuroprotective effects, but the mechanisms in vivo are unknown. We investigated apoptosis and apoptotic regulatory proteins in the brain frontal cortex of 12-month-old ad libitum fed, 26-month-old ad libitum fed, and 26-month-old calorie-restricted (CR) male Fischer 344 rats (CR = 40% restricted compared to ad libitum).