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-000972 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. When an NK cell is deficient or dysfunctional, the efficiency of the NK cells is severely limited. VISTA is a protein sequence that activates T cells and acts as a moderator for the immune system. It has low-to-moderate expression but has been the target of study by a team of researchers at Nationwide Children’s Hospital led by Dr. Dean Lee. By removing VISTA in expanded NK cells, the inhibitory signal will be eliminated and thus resulting in an enhanced ability of NK cells to target cancers and overcome the immune-suppressive signals for improved cancer immunotherapy.

TS-000643 — Gene therapy experts at Nationwide Children’s Hospital have made significant advancements in designing optimal viral vectors for producing Good Manufacturing Practice (GMP)-grade viral vector products. Our experts have optimized properties of vectors for a wide variety of Adeno-associated virus (AAV) serotypes, including AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74. In particular, our experts have optimized virus packaging efficiency, reduced potential to form replication competent AAV and replaced the beta-lactam resistant gene with kanamycin in order to be compliant with European Union (EU) regulations. Our experts have made additional optimized vectors for AAVrh74, and AAV9 that allow for more efficient purification and improved CNS transduction, respectively.

TS-000639 — Infectious recombinant Adeno-associated virus (rAAV) are exclusively used as gene transfer vehicles for an ever-widening array of human applications such as for use as vaccines and gene therapy vectors. A requirement for the clinical use of rAAV for DNA delivery is a highly efficient, reproducible and commercially scalable production. The most common methods of scalable rAAV production use HeLa cells. HeLa cells are derived from malignant cervical tumor and therefore, raises potential safety concerns. Gene therapy experts at Nationwide Children’s Hospital have developed new methods and materials achieving higher titers of rAAV in mammalian cells other than transformed cancer cells. This invention achieves scalable production of rAAV using clinically safe Vero cells derived from African green monkey kidney cells combined with the simian adenovirus 13 helper virus.

TS-000638 — One of the most promising forms of cancer gene therapy is delivery of genes directly to the tumor to facilitate cancer cell death. Gene therapy experts at Nationwide Children’s Hospital have developed a tumor-targeted novel molecular treatment by fusing two genes, Survivin and Granzyme B. Survivin is expressed at high levels in all tumors and Granzyme B induces apoptosis in tumor cells. The recombinant DNA is delivered to the target cells by another agent, such as liposome. This approach represents a universal method for targeting tumor cells that express Survivin and induce death of those cells, leaving minimal effect on healthy cells, unlike conventional chemotherapeutic approaches.

TS-000629 — Gene therapy experts at Nationwide Children’s Hospital have made significant advancements in designing optimal viral vectors for producing Good Manufacturing Practice (GMP)-grade viral vector products. Our experts have optimized properties of vectors for a wide variety of Adeno-associated virus (AAV) serotypes, including AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74. In particular, our experts have optimized virus packaging efficiency, reduced potential to form replication competent AAV and replaced the beta-lactam resistant gene with kanamycin in order to be compliant with European Union (EU) regulations. Our experts have made additional optimized vectors for AAVrh74, and AAV9 that allow for more efficient purification and improved CNS transduction, respectively.

TS-000627 — Gene therapy experts at Nationwide Children’s Hospital have made significant advancements in designing optimal viral vectors for producing Good Manufacturing Practice (GMP)-grade viral vector products. Our experts have optimized properties of vectors for a wide variety of Adeno-associated virus (AAV) serotypes, including AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74. In particular, our experts have optimized virus packaging efficiency, reduced potential to form replication competent AAV and replaced the beta-lactam resistant gene with kanamycin in order to be compliant with European Union (EU) regulations. Our experts have made additional optimized vectors for AAVrh74, and AAV9 that allow for more efficient purification and improved CNS transduction, respectively.

TS-000598 — CRIPSR/Cas9 gene editing technology is a promising tool for treating disease but requires the delivery of the large Cas9 enzyme. Gene therapy experts at Nationwide Children’s Hospital have taken two different approaches to couple the CRISPR gene editing machinery with AAV, including constructing Cas9 enzyme as a stable component of the AAV particle, as well as expressing Cas9 on the surface of the viral particle.

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