Gene therapy constitutes a promising novel modality for treatment of genetic diseases as well as cancer. However, widespread clinical adoption of gene therapies is still in its infancy not least due to various issues associated with using viral vectors to deliver transgenes to target tissues or tumors in patients. Therefore, non-viral delivery methods for DNA and possibly RNA could have advantages in terms of immunogenicity, toxicity, and more.
The aim of this project is to develop the next generation of non-viral DNA delivery tools using smart peptide nanoparticles specifically designed to carry theranostic agents comprising DNA and fluorescent molecules (as reporters), and to test them both in vitro and in vivo. We plan to implement extended nucleotide condensing sites of oligo histidines, and decrease the size of the self-assembled system below 50 nm.
Our study will provide a two-pronged strategy combining cutting-edge design of nanoscience based carriers with a suite of methods and assays that enable their detailed interrogation and understanding of their delivery mechanisms in vitro and in vivo. It will also form a basis for novel and expanded theranostic strategies due to co-entrapment of fluorescent molecules with large DNA payloads. This capability will, on one hand, enable the delivery of theranostic gene circuits; on the other hand, the entrapment of fluorescent dyes will enable facile readout of particle delivery in time and space that does not rely on gene expression. Importantly, this study takes advantage of established expertise and experimental capabilities in both collaborating labs.