Compositionally Defined Plasmid DNA/Polycation Nanoparticles and Methods for Making the Same

Unmet Need
Gene therapy can be a cure-all for genetic disorders, and can be a promising therapy for diseases such as cancer, neurodegenerative diseases, neurological disorders, heart disease or diabetes. The success of gene therapy is dependent on the safety, efficacy, and specificity of the treatment. The delivery vehicle, also known as a vector, is a highly enabling factor in the progression of better, safer, and more effective gene therapy. Non-viral vectors, compared to viral vectors, have a reduced risk of an immune response, mutation of the genes, have a flexible genetic load capacity, and can be engineered to target any cell. Non-viral vectors have an estimated market of $4.9 billion in 2023. However, the development of non-viral vectors into commercially realizable products has been slow non-viral vectors are not as effective as viral vectors. Improving the efficacy of non-viral vectors requires a highly uniform volume of vectors and a high degree of control over the surface properties, shape, amount of genetic material, and size of each individual vector. The lack of a controlled process for manufacturing non-viral vectors has resulted in a high variability in transfection efficacy, cell uptake, and cytotoxicity. Therefore, there is a need for a manufacturing and characterization process that gives control over multiple aspects of the final vector design in a predictable way. Reducing the variability in production of the delivery systems for gene therapies can improve the efficacy of gene therapy using non-viral vectors.

Technology Overview
The inventors’ technology can precisely tune the vector size, composition, and genetic payload of a non-viral vector using adjustable flow streams in a microchamber. Furthermore, this highly-controlled process has a 70% yield, high uniformity in the composition of the final solution, and low batch to batch variability. The non-viral vectors have a shelf life of over 9 months without any performance degradation and a reduced risk of immune response.

Stage of Development
The inventors have developed a well-characterized, two-stage process for manufacturing non-viral gene delivery nanoparticles with sizes ranging from 30 – 130 nm with varying genetic payloads. They have also achieved in vivo distribution within one hour and have results of gene transfection efficacy for nanoparticles with varying sizes, charge densities, and payloads.

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