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Rapidly dissolving biomaterials for high-efficiency viral transduction
Christopher Moody1, Pritha Agarwalla2, Micah Mallory2
1Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Dissolving Ultrafast Cell Transduction Sponges (DUCTS) enhance cell and gene therapy by improving genetic modification efficiency. This novel alginate cryogel technology works rapidly, reduces viral vector needs tenfold, and is compatible with various cell and virus types.
Area of Science:
- Biotechnology
- Genetic Medicine
- Cell Therapy Manufacturing
Background:
- Cell and gene therapies face bottlenecks due to inefficient genetic modification.
- Current viral vector delivery methods suffer from low efficiency and particle waste.
- Existing transduction enhancers have limitations, including narrow applicability, time-consuming protocols, or toxicity concerns.
Purpose of the Study:
- To introduce DUCTS (Dissolving Ultrafast Cell Transduction Sponges) as a novel solution to enhance viral vector-mediated cell transduction.
- To demonstrate the broad applicability and efficiency of DUCTS across different viral vectors and cell types.
- To address the critical need for improved efficiency, safety, and cost-effectiveness in cell and gene therapy manufacturing.
Main Methods:
- Development of DUCTS using uncrosslinked alginate cryogels.
- Testing DUCTS with gamma retrovirus, lentivirus, and adeno-associated virus (AAV).
- Evaluation of transduction efficiency in both suspension and adherent cells within a five-minute timeframe.
Main Results:
- DUCTS significantly boosts cell transduction efficiency across multiple viral vector types and cell cultures.
- Achieved comparable transduction efficiency using a tenfold reduction in viral vector concentration compared to standard protocols.
- Demonstrated rapid action (within five minutes) and complete dissolution of the material, simplifying workflows.
Conclusions:
- DUCTS offers a versatile, cell- and virus-agnostic platform for streamlining gene transfer procedures.
- This technology reduces viral consumption, lowers costs, and enhances the scalability of cell and gene therapies.
- Modified DUCTS can simultaneously activate and transduce T cells, potentially revolutionizing CAR-T cell manufacturing.
