Nanoparticle Delivery of Therapeutic NF1 Signaling ERPs to Schwann Cells

Recent advances in genome editing provide an opportunity to therapeutically address loss of the tumor suppressor gene neurofibromin 1 (NF1) and prevent neurofibromatosis type 1 (NF1). However, two key challenges remain to translate a NF1 gene therapy to the clinic: 1) development of a broadly applicable therapeutic approach for all individuals with NF1 rather than mutation-specific approaches, and 2) the ability to load and deliver large payloads (>4.7 kb) to specific cell types, such as Schwann cells. The overall goal of this project is to create targeted epigenetic regulatory proteins (ERPs) to be transient therapeutic payloads that cause persistent down-regulation of mitogen-activated protein kinases 1 and 2 (MEK1/2) and to deliver plasmid DNA (pDNA) encoding these ERPs to Schwann cells (SCs) in both human and mouse models. By combining the strengths of Battelle’s delivery platform with the University of California Davis’s payload expertise, this work will result in the development of a human-targeted ERP that can be tested in future studies in non-human primates (NHPs) as a candidate for therapy.