TS-001229 — Mutations in the Myotonic Dystrophy Protein Kinase gene (DMPK) cause an autosomal dominant inherited disease referred to as Myotonic Dystrophy. Myotonic Dystrophy affects more than 1 in 8,000 people worldwide. Myotonic dystrophy results in progressive muscle weakness, stiffness and wasting. Currently, here are no treatments for this disease. A team of researchers at Nationwide Children’s Hospital have designed short hairpin constructs of AAV-shRNA which can be used to silence DMPK mRNA and therefore potentially treat myotonic dystrophy.

TS-000597 — Recombinant adeno-associated virus (rAAV) is one of the most used viral vectors for gene therapy. However, large-scale rAAV production is labor intensive and costly due to the requirement for an efficient rAAV synthesis in stable cell lines. A team of researchers at Nationwide Children’s have developed a simple and cost-effective technique to ease the production of rAAV. Compared to existing methods, this approach allows more rAAV genomes to be encapsulated into infectious rAAV particles while allowing the production of rAAV in several cell types. The materials and methods of this invention are covered in the US issued patent 8,409,842.

TS-000513 — Dystrophinopathies are a group of disorders caused by mutations in the DMD gene which codes for dystrophin, the vital, muscle-specific structural protein. Currently, there is no cure for muscular dystrophy, and patients only rely on palliative care options. Our gene therapy researchers at Nationwide Children’s Hospital have developed an AAV-mediated gene editing method for correcting deleterious DMD mutations in affected patients. This therapy uses a homology-independent targeted integration (HITI) to replace any missing or aberrant exons in affected patients; therefore, correcting the underlying cause of DMD. This therapy will be developed to stop the progression of muscle wasting and fibrosis in individuals with DMD mutations that result in muscular dystrophy via permanent correct of the underlying cause within muscle tissue by replacing missing or aberrant exons using HITI. Advantages By developing AAV-Mediated HITI gene editing for correction of diverse DMD mutations in patients with muscular dystrophy, we can potentially cure BMD and DMD patients. These patients currently have no palliative care options. Our compositions of matter for this approach (i.e. genomic target region, guide-RNA sequences, donor DNA sequences) are new. Stage of Development Proof of concept studies completed Intellectual Property Provisional Patent Pending

TS-000500 — AAV mediated gene therapy is a promising therapeutic route for the treatment of inner ear disorders. However, finding a safe and effective delivery route for a gene therapy has been proven difficult to achieve as traditional routes of administration can cause additional damage to cells of the inner ear. To circumvent this challenge, researchers at Nationwide Children’s have explored the cerebrospinal fluid delivery route to prevent procedural damages. Our researchers have designed vectors to include cochlea-cell type promoters to achieve cell type specific expression and therefore have designed a subset of highly effective AAV gene therapy candidates to treat disorders affecting the inner ear. The invention is to use cerebrospinal fluid (CSF) as a delivery route for AAV mediated gene therapy to the cochlea. We found that CSF injections lead to spreading of AAV vectors throughout the entire nervous system as well as result in good targeting of the inner hair cells inside the cochlea. This could be particularly interesting for diseases that affect both the central nervous system as well as cells in the ear/cochlea. Moreover, the CSF delivery route could be used in combination with a cochlea-cell type specific promoter to achieve cell type specific expression. It is a new delivery route which could be combined with various gene therapy approaches for hearing disorders. The delivery route is promising because alternative delivery routes with injection directly into the cochlea often result in damage caused by the procedure. That damage could be prevented using the intrathecal CSF route. Thus, gene therapies delivered that way could be safer and more effective since damage could be avoided. Benefits: Many groups are working on a cochleal cell targeting of AAVs using intratympanic injections or injections directly into the cochlea as well as intravenous injections. We envision using the CSF as the delivery method of choice. State of Development: Pre-clinical Potential Applications/Markets: This invention has broad applications in the field of neurological and neurodegenerative disorders that also affect hearing, as well as for diseases that affect hearing by debilitating cells of the cochlea. Thus, there is potential for development of therapies for several diseases. Opportunity/Seeking: Development Partner Licensing Seeking Investment IP Status: Patent Application Submitted

TS-000497 — Huntington’s Disease (HD) is a late onset progressive neurodegenerative disorder that results in death in 10-15 years after the first sign of symptoms. Existing oligonucleotides (AONs) based therapies are imperfect as they knockdown wildtype protein, require consistent re-injections, and use potentially harmful molecules. Gene therapy experts at Nationwide Children’s have devised a gene therapy approach that uses a specific snRNA to stably and safely reduce the highly pathogenic protein HTT. By enabling a continuous expression of the therapeutic RNA in the nervous system (and other targets), this technology may delay the age of onset, slow symptom progression, and reduce symptom severity of HD. Hence, it has the potential to become the optimal therapeutic strategy for the treatment of HD.

TS-000470 — CuATSM is a small molecule which facilitates the delivery of copper to cells containing damaged mitochondria, the cell compartments responsible for the production of energy. Currently, CuATSM has shown success in clinical trials for treating patients with ALS. Neurodegenerative disease experts at Nationwide Children’s Hospital have elucidated novel mechanisms of action through which the small molecule can treat disorders caused by oxidative stress, mitochondrial dysfunction and elevation of stress response systems. Through these studies, our disease experts have identified several new indications which could be treated with this small molecule compound.

TS-000441 — Gene therapy experts at Nationwide Children’s hospital are utilizing adeno-associated virus (AAV) mediated gene therapy to target specific cell types within the retina to treat vision impairment, retinal degeneration and vision-related disorders. Although, use of ocular administration of gene therapy vectors has shown some promising results, there is a need for improved gene therapy methods. Our experts have designed various viral vectors, promoters, novel co-administration therapies and multiple delivery routes to target particular cell types in the retina. This preclinical study offers hope for treating vision loss. Benefits: This technology comprises different injection methods, different promoters, different viral vectors and combinatorial approaches. We have data which has enabled us to understand which viral vector/promoter/injection route combination works best for targeting of specific cell types in the retina. This will allow us to further improve gene therapy strategies for Batten Disease and for other disorders that cause retinal degeneration. Potential Markets/Applications: There are multiple groups working on AAV gene therapy for vision. The current methods are not sufficient to efficiently target bipolar cells in the retina. We are developing protocols and vectors that should be more efficient in targeting these cells as well as other cell types. Opportunity/Seeking: Development Partner Licensing Seeking Investment IP Status: Patent Application Submitted

TS-000438 — Gene therapy experts at Nationwide Children’s have developed an AAV-mediated CRISPR/Cas9 gene editing method for the correction of exon duplications in patients with DMD (Duchenne muscular dystrophy). This therapy has the potential to permanently corrects DMD by stopping and potentially reversing the progression of muscle wasting and fibrosis in affected individuals. Currently about 11% of DMD cases are caused by exon duplications and our experts plan to use this invention to correct for this underlying cause within muscle tissues.

TS-000392 — IRF2BPL-related disorders are a group of neurodegenerative disorders, characterized by abnormal movements, loss of speech, and seizures, and are caused by mutations within the IRF2BPL gene. Researchers at Nationwide Children’s have devised a gene therapy approach that uses adeno-associated viruses together with specific promoters to mediate the transfer of a functional gene in affected individuals. This approach ensures the restoration of the IRF2BPL protein which then leads to a drastic health improvement in patients. This Intellectual Property contains several products: - AAV vectors containing the IRF2BPL gene under the control of different promoters. - AAV vectors containing only the IRF2BPL coding sequence under the control of different promoters. The AAV.IRF2BPL gene transfer tested in this intellectual property is a new approach for IRF2BPL related disorders. It includes the IRF2BPL gene or its coding sequence under the control of different promoter to express IRF2BPL. These approaches were never explored for IRF2BPL related diseases. Stage of Development Proof of principle: Designed IRF2BPL sequences that force expression of human IRF2BPL gene. We also developed several in vitro assays to study the disease and the therapeutic vectors. We reprogrammed patient cell lines and made neuronal progenitor cells (NPCs) and astrocytes. Future Work: We intend to evaluate the effect of patient mutations on the expression level of IRF2BPL protein. We intend to use patient cells to test if AAV.IRF2BPL approaches allow restoration of a WT IRF2BPL protein following treatment with each AAV in vitro. We intend to inject the most promising constructs into mice. We will also inject the constructs in wild type mice to evaluate safety Potential Applications/Markets: These products will force expression of wild type IRF2BPL for any patients containing IRF2BPL related disorders. Therefore, this product has potential as a therapeutic. Opportunity/Seeking: Development Partner Commercial Partner Licensing University Spin Out Seeking Investment IP Status: Patent application submitted

TS-000358 — Congenital Muscular Dystrophy Type 1A (CMD1A) usually presents in the neonatal period with marked muscle weakness and severe hypotonia. CMD1A patients show deficiency in laminin-alpha2 (LAMA2) protein caused by the genetic mutations leading to weaker and unstable muscle tissue. Gene therapy experts at Nationwide Children’s Hospital have developed a gene and protein therapy approach enabling delivery of key domains of LAMA2 using adeno-associated virus (AAV). In addition, our experts have engineered fusion proteins that assist in anchoring LAMA2 to the muscle membrane thereby improving the muscle-matrix interaction and muscle integrity.