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-000969 — 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. Adeno-associated virus (AAV) serotypes such as AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74 have properties optimized by these researchers. Chimeric Antigen Receptor T cells (CAR T) are comprised of an extracellular antigen recognition domain, intracellular T cell activation and co-stimulatory domains. These cells allow for potent and specific targeting of cancer cells, bypassing the need for antigen presentation and T cell receptor recognition. Generating CAR T cells using the process of lentiviral transduction has limitations stemming from the random integration of transgenesis, where oncogene activation, gene silencing, or negative effects on the CAR T antitumor efficacy are possible.

TS-000852 — 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. Adeno-associated virus (AAV) serotypes such as AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74 have properties optimized by these researchers. The new plasmid named pscCMV-luc2P+ has several improvements including modifications that provide a significant improvement in packaging efficiency of AAV vectors, reduction in potential to form replication competent AAV and the inclusion of the ampicillin resistance gene. Dr. Scott Loiler and his team have made additional optimized vectors for AAVrh74, and AAV9 that allow for more efficient purification and improved CNS transduction, respectively.

TS-000851 — 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. Adeno-associated virus (AAV) serotypes such as AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74 have properties optimized by these researchers. The new plasmid named pNLRep-Cap1- Kan has several improvements including modifications that provide a significant improvement in packaging efficiency of AAV vectors, reduction in potential to form replication competent AAV and the inclusion of the ampicillin resistance gene. Dr. Scott Loiler and his team have made additional optimized vectors for AAVrh74, and AAV9 that allow for more efficient purification and improved CNS transduction, respectively.

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-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-000628 — 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-000626 — 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-000625 — 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-000391 — 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-000364 — Researchers at Nationwide Children's Hospital have identified modified capsid sequences of the Adeno-associated Virus rh74 (AAVrh74) native capsid that improve delivery of genes to specific target cells or overall global gene delivery. These include modifications that increase specific gene delivery to either the heart or muscle stem cells.

TS-000357 — 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-000354 — 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-000322 — 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-000307 — 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-000298 — Adeno-associated virus (AAV) vectors are replication defective viruses that are engineered to deliver therapeutic genetic cargo to cells. The structural and enzymatic AAV proteins are traditionally supplied “in trans” to generate engineered particles for gene delivery. One constraint of AAV vectors is the size limitation of the genetic insert. Gene therapy experts at Nationwide Children’s Hospital have engineered an AAV vector that expresses the Rep78 protein on the surface of the viral particle thus eliminating the need to package the rep coding region within the particle. This strategy allows for delivery of a functional Rep78 protein while increasing the overall therapeutic gene insert size.

TS-000290 — Adeno-associated virus (AAV) remains a leading viral vector candidate for gene delivery. However, the standard production of AAV makes use of ampicillin containing materials which can increase the risk of unwanted beta-lactam reactions in some sensitive patients. Researchers at Nationwide Children's have developed a novel plasmid, namely pHELP-kanV4, to replace the standard plasmid and allows for the production of recombinant AAV vectors without the chance of ampicillin gene or protein being retained as a contaminant in the final product. As a result, this will help increase the production of AAV for sensitive patients and especially in Europe where they is a strict guidance in the making of AAV.