partnership with the Interdisciplinary Neuroscience Program.
________________________________________________

 Register Here

*Zoom option available

Description

Autosomal dominant disorders present a distinct therapeutic challenge, especially when silencing the disease-causing transcript also reduces an essential protein. This talk highlights our AAV-mediated knockdown-and-replacement strategy which combines RNAi with gene replacement to suppress transcripts of a specific gene while restoring functional protein expression, independent of the underlying mutation. I will discuss its application to CMT1B and ACTA1-related nemaline myopathy, integrating patient iPSC-derived peripheral nerve organoids and cardiomyocytes, respectively, alongside mouse models to investigate disease mechanisms and evaluate therapeutic efficacy. Through this work, we have developed mutation-agnostic therapies for CMT1B and ACTA1-related nemaline myopathy with strong translational potential, while laying the groundwork for adapting this platform to other inherited disorders caused by dominant mutations in essential genes.

Speaker 

Areas of Expertise

• Gene Expression
• Molecular Medicine
• Molecular Neurobiology

Afrooz Rashnonejad, MSc, PhD is an Assistant Professor of Pediatrics at The Ohio State University College of Medicine and a Principal Investigator at the Jerry R. Mendell Center for Gene Therapy at Nationwide Children’s Hospital (NCH). Her research focuses on developing adeno-associated virus (AAV)-based gene therapies for neurological and neuromuscular diseases. As part of her doctoral work, she developed a prenatal gene therapy approach for Spinal Muscular Atrophy (SMA) under the mentorship of Dr. Ferda Ozkinay (Ege University, Izmir, Turkey) and Dr. Guangping Gao (Director of Gene Therapy Center, UMass Medical School, MA). She later completed her postdoctoral training at the Center for Gene Therapy at NCH in Dr. Scott Harper’s lab, where she developed RNA-targeting therapies, including AAV-U7snRNA and AAV-CRISPR-Cas13, and miRNA- mediated gene therapies for FSHD. Her independent laboratory develops therapies for neurological and neuromuscular diseases, including CMT1B, nemaline myopathy, and RYR1-related myopathies, by combining iPSC-derived organoid models with RNAi, gene replacement, and RNA end-joining strategies. Dr. Rashnonejad served on multiple scientific committees, including chairing ASGCT’s New Investigator Committee and serving on the Musculoskeletal Cell and Gene Therapy Committee and the Prenatal Cell and Gene Therapy Committee. She was honored to receive the ASGCT Excellence in Research Award in two consecutive years, 2019 and 2020. Dr. Rashnonejad also serves on the scientific advisory boards of patient foundations.