Structural design of polymeric nanocarriers to enable mRNA-based cancer vaccine technologies

Messenger RNA (mRNA)-based cancer vaccines is a technology with tremendous potential to enable personalized cancer treatments.

This strategy requires intracellular delivery of mRNA encoding cancer specific antigens to antigen presenting cells (APCs) to elicit a cytotoxic T cell response towards the cancer cells.

However; mRNA molecules are not able to enter cells by themselves; thus, delivery technologies are needed to realize their transformative potential.

I will design biodegradable polymeric nanoparticles with lipid subunits incorporated in their structure for amphipathic properties to enable efficient intracellular mRNA delivery to APCs (Aim 1). Additionally, activation of APCs is required for potent immune responses against the cancer cells.

To address this, I will synthesize polymeric nanocarriers incorporating structural components mimicking adjuvants for biomaterial-mediated activation and engineer nanoparticle formulations for co-delivery of mRNA and adjuvants to induce APC activation (Aim 2). The engineered nanoparticles will be administrated systemically to facilitate the highest expression of the neoantigen.

I will incorporate photo-crosslinking for improved nanoparticle stability and surface functionalize nanoparticles with mannose for targeted delivery to APCs (Aim 3).

I will through these design principles develop the next-generation of nanocarriers for efficient intracellular mRNA delivery to APCs in order to realize mRNA-based cancer vaccine technologies.