Unmet Need
Gene therapy has the potential to provide effective treatment options for a variety of monogenic human diseases [1].Viral-mediated gene therapy has seen some clinical success, including the recent FDA approval of therapeutics for retinal dystrophy and spinal muscular atrophy [2]. However, viral mediated therapies can have unwanted side effects, including immunogenicity and oncogenesis [3, 4]. Lipid nanoparticles can be used as safe, alternative carriers for transgene delivery, but their utility has been limited by poor transfection efficiency [3, 4]. In addition, there are currently no large-scale production methods for generating stable, off-the-shelf DNA/lipid particles of consistent quality [4]. Therefore, there is a strong need to identify mechanisms that increase the transfection efficiency of DNA/lipid nanoparticles and to develop production methods that improve product yield and consistency.
Technology Overview
Researchers at Johns Hopkins have identified the optimal size of plasmid DNA/lipid particles required for efficient cell transfection. In addition, they have developed scalable methods for size-specific nanoparticle assembly, based on kinetic control of particle aggregation. This technology allows for large-scale preparation of shelf-stable nanoparticles of a defined size, which can be tailored within a range. These methods can streamline manufacturing, increase yields, and improve quality in the industrial production of nanoparticle-based gene therapies with enhanced transfection efficiency and reproducibility.
Stage of Development
Proof-of-concept technology has been developed, demonstrating improvements in transfection efficiency in vitro and in vivo. Validation of scalability and continued demonstration of utility are in progress.
Publication
Manuscript in preparation
