Topic: transgene expression

Creatine Transporter Deficiency (CTD) is a rare X-linked disorder caused by loss-of-function of the SLC6A8 gene. CTD clinical manifestation follows brain creatine (Cr) deficiency and predominantly leads to neurological symptoms such as intellectual disability, language disturbance, psycho-motor impairment, autistic-like behavior, and seizures. We used a murine model to probe whether perinatal adeno-associated virus (AAV)-mediated expression of a functional SLC6A8 transgene under the control of a ubiquitous promoter could restore creatine transporter (CRT) expression and brain Cr level, thus pr

Adeno-associated virus (AAV) vectors are the principal vehicle for gene therapy. In a large share of humans, immunity against AAVs can reduce or completely inhibit transgene expression, and can lead to adverse outcomes. The level of immunity can be estimated by assaying AAV neutralization level of the blood serum. Surprisingly, there is no widely adopted sensitive assay for the quantification of AAV neutralization.Results: We developed an in vitro neutralization assay, and quantified its reproducibility and sensitivity via longitudinal evaluation of neutralization in preclinical models and hum

The locus coeruleus (LC) noradrenergic (NE) system is involved in a plethora of physiological and pathophysiological processes. Refining our understanding of LC function largely relies on selective transgene expression in molecularly defined cells, allowing targeted manipulation and readout of noradrenergic neurons. Here, we performed a side-by-side comparison of the most commonly used strategies to genetically access the LC, including different cre driver lines and promoter-mediated transgene expression. We report differences between these strategies in terms of transgene expression efficacy