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-004703 — For AAVs that harbor gene knockdown machinery, this IP is a novel potency assay development for release testing that creates a HEK293T stable cell line to integrate two genetic components.

TS-004612 — This IP is a therapeutic strategy for facioscapulohumeral dystrophy (FSHD), which is associated with an inappropriate expression of DUX4. Using dual AAV split-intein vectors, it expresses full-length SMCHD1, enhances epigenetic silencing and reduces DUX4 toxicity.

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-004598 — This system may help improve the safety of AAV vector products by decreasing cross-packaged bacterial sequences, increasing correctly packaged AAV payloads and blunting ITR-driven transcription of cross-packaged material to avoid expressing potentially toxic bacterial sequences.

TS-004596 — There's a signficiant unmet need among thousands of Americans who struggle with genetic neuromuscular disease; this one-time AAV-delivered proprietary engineered miRNA targets core disease biology, specifically in Facioscapulohumeral Muscular Dystrophy (FSHD). This durable gene therapy reduces immunogenicity by taking advantage of nature’s highly active gene regulation biology.

TS-002356 — Education coordinator, Adrianna Matos-Nieves, PhD, at Nationwide Children’s Hospital created an educational board game called Viruses and Vaccines. The board game teaches the benefits of vaccines, the danger of contracting diseases, and the impact of future health decisions. The gamification of vaccine learning makes it the perfect educational tool for parents and children. The game illustrates a long healthy lifespan by going up a ladder and diseases with no prior vaccination or vaccine push the player down a ladder with each space having corresponding card of information about the vaccine and disease. Viruses and Vaccines encourages players to make informed decisions about their health to promote healthy living.

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-002303 — WHO: Scott Harper WHAT: RNAi therapy WHY: DNM1 Developmental and Epileptic Encephalopathy (DEE) HOW: (from IDF) The DNM1 gene encodes dynamin-1, a large GTPase involved in clathrin-mediated endocytosis of synaptic vesicles in neurons and in related processes. Dynamin monomers assemble into multimers that interact with each other and with various other proteins to form ring structures for GTPase-catalyzed membrane scission. Dominant mutations in one allele of DNM1 cause neurological disease in humans and mice. Children with DNM1 mutations suffer from intractable conditions manifesting as early-onset seizures, global developmental delay, profound intellectual disability, lack of speech, muscular hypotonia, dystonia, and spasticity. As is the case with many severe DEEs, affected individuals do not respond well to antiepileptic drugs, leaving >80 % of patients with intractable seizures and little to no improvement of the severely debilitating other neurological features. At least 20 de novo pathogenic DNM1 variants have been identified, and all are presumed to operate with dominant effect, most likely by interfering with the assembly or function of normal dynamin-1 monomers. Importantly, knockout studies in mice support that at least 50% normal DNM1 levels are required, as homozogous DNM1 null animals die by postnatal day 8. We propose that a successful gene therapy approach must eliminate or reduce the expression or translation of the mutant DNM1 variant mRNA or protein, while still enabling expression of the remaining wild-type allele. We are pursuing two different approaches to accomplish this: (1) isoform-specific silencing of mutant DNM1 transcripts; (2) a knockdown-and-replace strategy; expressing exogenous wildtype Dnm1 via AAV while eliminating endogenous Dnm1 mRNA entirely. We already filed an IDF and provisional patent application on approach 1. This IDF covers the knockdown-and-replace strategy. In brief, we will develop artificial microRNAs that non-selectively knockdown both mutant and wild-type DNM1 alleles using RNAi, while at the same time adding back an RNAi-resistant, wild-type DNM1 cDNA. We will test this in mouse models of DNM1-related DEE in the Frankel lab at Columbia University.