Articles by Naemeh Pourshafie in JoVE
Systemisk levering af mikroRNA ved hjælp af rekombinante Adeno-associeret Virus Serotype 9 til behandling af neuromuskulære sygdomme i gnavere Naemeh Pourshafie1, Philip R. Lee2, Ke-lian Chen1, George G. Harmison1, Laura C. Bott1,3, Kenneth H. Fischbeck1, Carlo Rinaldi1,4 1Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 2Section on Nervous System Development and Plasticity, The Eunice Kennedy Shriver National Institute of Child and Human Development, National Institutes of Health, 3Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, 4Department of Physiology, Anatomy and Genetics, University of Oxford Her beskriver vi levering af mikroRNA ved hjælp af en rekombinant adeno-associeret virus serotype 9 i en musemodel af neuromuskulære sygdomme. En enkelt perifere administration i mus resulteret i vedvarende miRNA overekspression i muskel og motoriske neuroner, giver mulighed for undersøgelse miRNA funktion og terapeutiske potentielle in vivo.
Other articles by Naemeh Pourshafie on PubMed
MiR-298 Counteracts Mutant Androgen Receptor Toxicity in Spinal and Bulbar Muscular Atrophy Molecular Therapy : the Journal of the American Society of Gene Therapy. 05, 2016 | Pubmed ID: 26755334 Spinal and bulbar muscular atrophy (SBMA) is a currently untreatable adult-onset neuromuscular disease caused by expansion of a polyglutamine repeat in the androgen receptor (AR). In SBMA, as in other polyglutamine diseases, a toxic gain of function in the mutant protein is an important factor in the disease mechanism; therefore, reducing the mutant protein holds promise as an effective treatment strategy. In this work, we evaluated a microRNA (miRNA) to reduce AR expression. From a list of predicted miRNAs that target human AR, we selected microRNA-298 (miR-298) for its ability to downregulate AR mRNA and protein levels when transfected in cells overexpressing wild-type and mutant AR and in SBMA patient-derived fibroblasts. We showed that miR-298 directly binds to the 3'-untranslated region of the human AR transcript, and counteracts AR toxicity in vitro. Intravenous delivery of miR-298 with adeno-associated virus serotype 9 vector resulted in efficient transduction of muscle and spinal cord and amelioration of the disease phenotype in SBMA mice. Our findings support the development of miRNAs as a therapeutic strategy for SBMA and other neurodegenerative disorders caused by toxic proteins.