Gene modified autologous hematopoietic stem cell transplantation is a transformative approach for treating variety of blood cancers and immunodeficiency disorders. However, the current methods for therapy manufacture need substantial quantities of costly GMP grade viral vectors to deliver the nucleic acids for deriving therapeutic cells. The high cost and limited supply of GMP grade vectors contributes to large expenses incurred by patients as well as long waiting lists which delay patient treatment. Additionally, vector availability to clinical researchers developing new therapies is also reduced which slows clinical translation. While other non-vector- based methods for nucleic acid delivery are available, they have disadvantages in working with delicate stem cells such as low cell viability and highly delivery efficiency which limits their clinical applicability. Ferrologix proposes to develop a modular product that can achieve a ?10 fold reduction in the quantity of vector necessary to produce a therapeutic cell batch compared to the current co-culture methods. Utilizing arrays of ferromagnetic micropillars, magnetically tagged target cells and viral vector can be concentrated to discrete points for highly controlled exposure. By confining the volume of cells and vector, precision vector mediated nucleic acid delivery can be achieved. In this phase I submission we propose to develop a magnetic transduction platform that can significantly reduce per batch vector consumption, which can lead to more rapid clinical translation of new therapies and scaled patient treatment capabilities.
Public Health Relevance Statement: Project Narrative The goal of this project is to develop a magnetic based nucleic acid delivery platform which can reduce consumption viral vector for autologous stem cell therapies. The limited supply and high cost of vector translates to significant cost and treatment delays for patients as well as impeding research for new treatments. Current techniques and technologies either require large quantities of vector to manufacture the therapy, are too harsh for use with stem cells, or have limited precision. Our proposed technology can reduce the required vector usage in a gently way, translating to accelerated research and improved patient outcomes.
NIH Spending Category: Biotechnology; Gene Therapy; Genetics; Regenerative Medicine; Stem Cell Research; Stem Cell Research - Nonembryonic - Human; Transplantation
Project Terms: Autologous; base; CD34 gene; Cell Survival; Cell Volumes; Cells; Cellulose; Clinical; clinical application; clinical translation; Coculture Techniques; Consumption; cost; Dependovirus; design; Disadvantaged; Dose; experimental study; ferrite; Flow Cytometry; Fluorescence Microscopy; Gene-Modified; Genetic; Genetic Vectors; Geometry; Glass; Goals; Gold; Hematopoietic Neoplasms; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Immunologic Deficiency Syndromes; improved; Lead; Magnetism; Measures; Mediating; Methods; Modification; novel therapeutics; nucleic acid delivery; Nucleic Acids; particle; Patient-Focused Outcomes; Patients; Performance; Phase; Planet Earth; Protocols documentation; Reagent; Research; Research Personnel; Running; stem cell therapy; Stem cells; Sterility; System; Techniques; Technology; Therapeutic; therapy development; Time; Transfection; Translating; vector; Viral Vector; Virus; Waiting Lists
