Peeler Lab Research

Although it is known that the structure of lipid nanoparticles can be engineered to augment stability and transfection, the broader chemical and structural diversity of polymeric RNA delivery materials remains largely untapped. We are using high-throughput synthesis, formulation, and characterization methods to generate ML-interpretable datasets that evolve transfection formulations with desirable properties for specific applications. High-performing formulations serve as the basis for more detailed structure-function studies using fluorescence correlation spectroscopy (FCS), small angle scattering (SAXS/SANS), and molecular dynamics modeling (MD).

While innate immunogenicity is a well-documented barrier to therapeutic RNA applications, we are just beginning to understand how delivery formulations modulate human innate responses to transfection. We use human skin explant cultures and others to study connections between formulation chemistry, endocytosis, and danger sensing to engineer more effective RNA immunotherapies with fewer side effects.

Targeting the delivery of immunomodulatory drugs can engineer immune response that alter the effects of co-delivered therapeutics. For example, we have shown that lymph node targeted STING agonism extended saRNA transfection from polymeric nanoparticles by dampening cytotoxic T cell responses. We are exploring where and when drugs can be delivered to modulate RNA expression and innate responses for therapeutic benefit.