TS-005789 — This novel vitro, cell‑based potency assay for evaluating adeno‑associated virus (AAV)–mediated gene therapies targeting muscle disorders, particularly those utilizing AAV9 vectors. This represents a significant improvement in potency determination workflows, providing a reproducible, scalable, and regulatory‑relevant alternative to animal‑based assays for muscle‑directed gene therapies.

TS-002317 — FOXG1 syndrome is a rare neurological and developmental disorder that usually affects children at infancy. Individuals with this disorder experience seizures, delayed development, intellectual disability, and mobility issues. Currently, there is no cure. Researchers at Nationwide Children’s Hospital designed a conventional gene therapy approach for FOXG1 by establishing vitro models and comparing data for FOXG1 cell lines and Rhett Syndrome cell lines. (need info. about the results of the 2021 pilot study)

TS-002279 — What: gene therapy for pediatric epileptic encephalopathy resultant from mutations in SLC6A1 gene Six new gene replacement products New shRNAs for gene knockdown New delivery route and dosing ranges Why: pediatric epileptic encephalopathy Current treatment is limited to symptomatic treatment, primarily by use of antiepileptic drugs How: single stranded AAV serotype 9 that will provide a wildtype copy of SLC6A1 to address haploinsufficiency resultant from mutations in one copy of the SLC6A1 gene Delivered through cerebrospinal fluid (CSF) via injection

TS-002230 — Currently, targeting the retina is difficult due to the thickness of vitreous preventing easy diffusing to the retina and restricted access due to the inner-limiting membrane (ILM). These challenges are especially difficult in the context of retinal AAV therapies. Researchers at Nationwide Children’s Hospital propose using Omnipaque to increase the density of injection solutions containing AAVs to allow for increased delivery to the retina combined with supine positioning of the patient. This addition would eliminate the need for risky, complicated injection methods.

TS-002229 — Adeno-associated virus vectors (AAV) are used to deliver normal copies of genes or therapies to a targeted tissue or organ as treatment for many genetic disorders. Researchers at Nationwide Children’s Hospital created a process that will improve the production process for AAV viral vectors in flatware and bioreactors for suspension and adherent cells. They performed placid transfection prior to seeding into the tissue culture flasks which decreased the incubation time for cells in the bioreactor and yielded a higher crude AAV viral vector yield by 8-10-fold. Therefore, this process will reduce production time and costs of production.

TS-002224 — Researchers at Nationwide Children’s Hospital developed a new technology to regulate gene expression. They propose utilizing U7 small nuclear RNA with a tail will attract endogenous activator or pressor proteins. The U7 small RNA will guide RNAs to bind to promoter sequences to alter gene expression by blocking activator or repressor elements in promoters. The attached tail will consist of specific binding sequences recognized by the repressor or activator proteins attracting them to the intended promoter for its regulation.

TS-002223 — Amyotrophic Lateral Sclerosis (ALS) is a neurogenerative disease that impacts the nerve cells of the brain and spinal cord causing muscles to weaken and affecting physical function. Researchers at Nationwide Children’s Hospital have created a therapy approach to reduce the expression of the superoxide dismutase 1 gene (SOD1). The gene therapy combines the usage of AAV small hairpin RNA sequences (shRNA) and U7 small nuclear RNA (snRNA). The C9ORF72 repeat expansion is the known leading cause of ALS. The AAV shRNA will downregulate the SOD1 gene and fight against the C9ORF72 expansion while the U7 snRNA will induce exon skipping of the SOD1 mRNA and C9ORF72 repeat expansion to create an out of frame skipping that will degrade the transcripts. Combining the two approaches into a single vector could create an efficient gene therapy for ALS while treating a larger patient subpopulation.

TS-002095 — About 3 of every 100,000 births are affected by Batten disease, a disorder that prevents the body from removing cellular waste like lipids and proteins. The build up of cellular waste throughout the body can cause seizures, vision loss, delays in thinking, abnormal movements and death. Researchers at Nationwide Children’s Hospital created a new intrathecal gene therapy using Adeno-Associated viral vectors for Batten Disease caused by mutations in the CLN8 gene. They generated an Adeno-Associated viral vector serotype 9 (AAV9) that contains the human CLN8 cDNA driven by a promoter.