TS-004705 — Modified GNPs offer a promising avenue for therapeutic interventions in the field of rare neurological disorders, providing insights into their effectiveness at the cellular level and offering potential avenues for clinical applications.

TS-004606 — For patients with NF2-related Schwannomatosis, there's currently no FDA-approved treatment drug available. Using Nelfinavir, an existing FDA-approved drug, will efficiently and safely block retroviral protease activity. This anti-retroviral drug reduces the growth of existing tumors and prevents/slows the generation of new tumors.

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-002304 — Researchers at Nationwide Children’s Hospital have created a new, improved method of mRNA exon replacement for any disorder through the combination of a transplicing molecule (PTM) and U7 small nuclear RNA constructs exon skipping tool in an AAV vector. To establish proof of concept, the team tested for mutations in exon 1 and 1 of the SCN2A gene. Two constructs will mediate both exclusions of the endogenous exons 1-2, where one bears a disease-causing mutation, and swaps them with a wild type or enhanced exon 1-2 transplicing molecule. A self-complementary (sc) and/or single stranded adeno-associated virus (AAV) serotypes that target the central nervous system and muscles will deliver the combined approach. These first two products force replacement of mutated SCN2A exon 1-2 for a subpopulation of patients affected by SCN2A disorders. This combination shows immense potential application in its replacement of any mutated mRNA piece.

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-002231 — About 1 in 50,000 people in the United States are affected by Friedreich’s Ataxia, an inherited disorder caused by a gene which damages the nervous system causing difficulties walking, slow speech, fatigue and sensation changes. Researchers at Nationwide Children’s Hospital developed an innovative way to modulate promoter activity to alter Frataxin gene expression using U7 small nuclear RNA. The U7 snRNA has mammalian origin, can have sustained and stable expression as it acts as a promoter and is safe for human patients. Additionally, the method suggests using U& snRNA with a tail to attract endogenous activator proteins which bind to DNA. The method can be combined with other gene replacement strategies to add additional U7-activators and using promoter regulation to activate promoters to upregulate a gene expression of a certain gene like Friedreich’s Ataxia.

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-002225 — Gene therapy researchers at Nationwide Children’s Hospital created an AAV medicated gene therapy for the treatment of neurological, neuromuscular and muscular disorders like SCN2A, Duchenne Muscular Dystrophy, Pitt Hopkins Syndrome, etc. Their therapy suggests using AAV gene therapy to deliver tRNA to read through premature stop codons caused by missense mutations preventing protein truncation. Multiple tRNAs will be inserted in an AAV construct to target multiple mutations. The therapy will effectively deliver genes of interest to the target cell types and can be adapted to other disorders through changing serotypes to switch targeted cell types.

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.