Service Project #6: Polymer Nanoparticles for Delivery of Nucleic Acids to the Retina 

Collaborating Investigator: Raffaella Toso
Affiliation: Spark Therapeutics
Funding Status: Internal
Project Period: 01/19/19-12/31/25 

Summary

The goal of SP #6 is to use non-viral nanoparticle delivery vehicles for gene transfer to the retina. Spark Therapeutics is a leader in ocular gene therapy, including an FDA-approved ocular viral gene therapy commercial product, and is interested in also investigating alternative carriers that could have advantages such as accommodating larger payloads of nucleic acids. Polymeric NIM particles created in TR&D2 Aim 1 will be evaluated by Spark Therapeutics for ocular applications of gene therapy. Spark will provide feedback on the outcome of their evaluation. As long-term gene expression in animals (>1 year) is desired, this evaluation project will take multiple years, but with positive data, it has the potential to grow to be a CP in the future. Data from the studies will be disseminated and published.  

Approach

Aim. Evaluation of nanoparticle materials for use in ocular gene delivery.  This aim is focused on evaluation of the nanomaterials for gene delivery to a different cell target, photoreceptors and retinal pigment epithelial cellsA selection of nanoparticles will be evaluated in vitro and then in vivo in rodents. Spark will perform ocular injections in rodents to evaluate for safety, efficacy, and durability. It is anticipated that this SP will enable the NIM materials to be used for new applications that are also important for human health and the treatment of diseases.  

NIMs will be synthesized as described in TR&D2 Specific Aim 1 then shipped to Spark Therapeutics for in-house analysis. Plasmid DNA delivery and expression will be evaluated in rodent models following ocular injections. Initially GFP plasmid will be evaluated by fluorescence expression, and if this is positive, other genes of interest can be explored.

TRD