Precision Medicine Center for Cystic Fibrosis

ABSTRACT/PROJECT SUMMARY (VIRAL AND NON-VIRAL VECTOR CORE – CORE 2) The Viral and Non-Viral Vector Core (VNVVC) serves multiple projects directed at the study of therapy development. The interaction with multiple investigators from various disciplines allows for cross-fertilization of ideas, technical advancements, and innovations in vector designs. This VNVVC provides novel systems for genetic complementation of pathogenic variants and advancement of potentially life-long curative therapeutic strategies. Responsibilities of this Core include consulting with the researchers, developing novel vectors, preparing routine vectors, and archiving materials. The VNVVC staff and investigators are in close contact through all phases of vector design and generation. Thus, this Core serves as both a research and development facility for gene transfer studies and a service facility for routine vector preparations. For gene delivery, the VNVVC provides purified and concentrated preparations of recombinant viral and non-viral vectors such as adenovirus (Ad), helper-dependent adenovirus (HDAd), adeno-associated virus (AAV), virus-like particles (VLPs), lipid nanoparticles (LNPs), and lentivirus (LV), as well as more specialized vectors such as vaccinia virus. These vectors have proven success at delivering CRISPR-based technologies to airway cells. For example, we produce multiple vector platforms to deliver an adenosine deaminase fused to a CRISPR-Cas9 nickase (termed an Adenine Base Editor (ABE)) to achieve site-specific repair. We also generate genetically modified cultured cells, which is a new service with wide utility. Additional services include access to standard cell lines, expression plasmids, and stocks of reporter viruses. This facility serves the needs of numerous outside investigators interested in both basic and applied gene therapy research. A continuum of new ideas from both outside and within the university ensures that the P30 Center Members have access to state-of-the-art methodologies, technologies, and reagents necessary for CF therapy development. In summary, the main responsibilities of the VNVVC are: 1) production of viral and non-viral vectors; 2) research and development; 3) education; and 4) archiving of materials.