The fields of gene therapy and bacteriophage therapy are rapidly expanding and show promising potential for treating genetic disorders and antibiotic resistant bacterial infections, respectively. To meet these needs, improved high throughput and high affinity viral purification methods will be required. Current high throughput viral purification methods mainly consist of resin-based chromatography coupled with multiple filtration steps. Chromatography-based methods often lack specificity for the particular virus target. For example, the commonly used ion exchange resins are not able to separate contaminants sharing similar surface net charges to the virus particles. Selection of mixed virus varieties such as viruses of different serotypes cannot be achieved with chromatography methods. Affinity-based resin chromatography products targeting viral vectors exist but are expensive or not suitable for large-scale purification. Additionally, they involve coupling a binding entity to resin, which presents several disadvantages, including leaching of the affinity ligand from the chromatography support or the ligand co-eluting with the virus particles. Thus, improved methods for simple, rapid, and scalable purification of viral vectors are needed to serve both the small-scale research community and large-scale industrial production. Bondwell Technologies proposes to develop a novel purification system for large biomolecules, such as viral vectors. The unique qualities of our functionalized biomaterial provide tremendous versatility and addresses the current limitations of small- and large-scale viral purification. During this proposed Phase I effort, we will first functionalize our biomaterials with an entity capable of specifically recognizing a viral target. We will then test the biomaterial for their ability to bind the viral target. Finally, we will prepare our biomaterial to be used as a membrane and test its ability to bind a viral target with different complexities of starting material (e.g., with cellular debris present).
Public Health Relevance Statement: PROJECT NARRATIVE The fields of gene therapy and bacteriophage therapy are rapidly expanding and show promising potential for treating genetic disorders and antibiotic resistant bacterial infections. To meet these needs, improved methods for simple, rapid, and scalable purification of viral vectors are required to serve both the small-scale research community and large-scale industrial production. Current methods either lack target specificity, are not suitable for large-scale or are very expensive.
Project Terms: Adenoviridae; Adenoviruses; Air; Antibodies; Bacterial Infections; bacteria infection; bacterial disease; Bacteriophages; Phages; bacterial virus; Biocompatible Materials; Biomaterials; biological material; Buffers; Charge; Chromatography; Communities; Disadvantaged; Feasibility Studies; Filtration; Filtration Fractionation; gene therapy; DNA Therapy; Gene Transfer Clinical; Genetic Intervention; gene repair therapy; gene-based therapy; genetic therapy; genomic therapy; Housing; Ion Exchange Resins; Ligands; Methods; Proteins; Research; Plant Resins; resin; Serotyping; Specificity; Syringes; Tandem Repeat Sequences; Tandem Repeats; Technology; Testing; Time; Virion; Virus Particle; Virus; Viscosity; Water; Hydrogen Oxide; Work; dityrosine; bityrosine; o,o-dityrosine; Film; Chimera Protein; Fusion Protein; Chimeric Proteins; crosslink; improved; Surface; Phase; Ensure; Fiber; Therapeutic; Mechanics; mechanic; mechanical; System; Viral; covalent bond; Membrane; membrane structure; monomer; protein purification; success; Recipe; Proxy; novel; Property; Bacterial Antibiotic Resistance; antibiotic resistant bacteria; bacterial antibiotic resistant; bacterial resistance to antibiotic; Drosophila Proteins; Molecular Interaction; Binding; Address; Affinity; Molecular Biology Techniques; Gene Transduction Agent; Gene Therapy Vectors; Gene Transduction Vectors; Viral Vector; Characteristics; Process; cost; Consumption; Coupled; Coupling; innovate; innovative; innovation; Electrospinning; genetic condition; genetic disorder; Genetic Diseases; industrial production
