Research Objective: Harness engineering principles to control the physical, chemical, and biological properties of nanoimmunomaterials (NIM) for cellular engineering.

Technology Outcome: Nanobiotechnologies that target and engineer immune effectors (dendritic cells, T cells, and macrophages) in vivo in a targeted, cell-specific fashion.

The goal of TR&D 2 is to bioengineer nanoimmunomaterial tools (NIMs) through the design and synthesis of new biomaterials and nanoparticles (NPs) created for immunomodulation. To do this, our three specific aims are:

• Specific Aim 1: Engineer the chemistry of NIMs for targeted intracellular delivery of nucleic acids to dendritic cells (DCs) and utilize them to construct next-generation vaccines.
• Specific Aim 2: Engineer the physical size of NIMs for improved mRNA loading, targeted delivery, and immunomodulation of macrophages.
• Specific Aim 3: Engineer the biological surface of NIMs for in situ targeting and genetic engineering of T cells.

We will engineer NIMs’ chemical structure, physical properties, and surface coating with biologics to maximize cell-specific intracellular delivery of nucleic acids to program immune cells. Specifically, we focus on genetically engineering three types of immune cells: dendritic cells for improved genetic vaccines; in situ macrophage programming; and in situ T cell programming. This includes applications to stimulate or suppress reactivity to antigens in vivo in a targeted, cell-specific fashion. NIMs will be evaluated for applications to human health, including oncology and autoimmunity.