# Modular Toolbox of Protein and Lipid Hybrid Biomaterials for siRNA Delivery > **NIH NIH R01** · NEW YORK UNIVERSITY · 2024 · $545,162 ## Abstract ABSTRACT/PROJECT DESCRIPTION: Technologies for gene delivery are desperately needed to address a wide array of pathological processes in the various tissues of the body. In particular, effective therapies for diabetic skin wounds poses a significant clinical and scientific challenge due to heightened health care costs and increasing incidence of diabetes worldwide. Recent progress in biomaterial-based gene delivery has ushered in promising options to treat chronic wounds via localized effects; however, degradation or interception of precious nucleic acid therapeutic cargo in transit— especially after unsuccessful escape from their endocytic vesicle—contributes to underwhelming transfection efficiencies that render these technologies insufficient for clinical translation and an unmet need. The overall objective of this proposal is to construct a modular arsenal of versatile, multi-functional supercharged proteins and lipids that can be co-formulated into a hybrid nanovehicle, termed lipoproteoplex (LPP), for the delivery of short interfering RNA (siRNA) sequences. We seek to improve the efficiency and safety of the LPP technological platform by delving into its unique mechanism of cellular entry and cytosolic uptake. We propose the central hypothesis that engineered proteins serve as the core, functional component of the LPP, dictating cargo binding strength, whereas the outer lipid component serves to protect the payload. Both items collectively contribute to and influence the bulk LPP's mechanism of cellular entry and cytosolic uptake. By harnessing a computationally- informed experimental approach, we will generate novel cationic supercharged protein sequences and study their interactions with various lipid shells to enhance the overall effectiveness of our LPP platform technology for siRNA delivery. We will pursue this optimized formula through the following specific aims: (1) expand the cationic supercharged protein library with viral tagged mutants to maximize the amount of endosomal escape while balancing gene binding capabilities; (2) evaluate the role of the LPP's outer liposome on payload protection and vehicle self-assembly; and (3) elucidate the LPP's cellular uptake mechanism essential for efficacious delivery of siKeap1 in a murine humanized diabetic wound model. The expected outcome of this proposal is an adaptable LPP formulation optimized to address the critical disease model of diabetic ulcers and wounds by promoting wounded skin repair in a pre-clinical hyperglycemic environment. Beyond the proof-of-concept validation model, the long-term goal of our work is to rationally design the LPP formulation for other siRNA sequences to have a positive translational impact on a wide array of monogenic cutaneous disorders. While other approaches focus on chemically modifying the vehicle, our innovative approach focuses on the LPP's easily-modulated and scalable components as the key driver of nucleic acid loading and subsequently successfu... ## Key facts - **NIH application ID:** 10979533 - **Project number:** 1R01EB035146-01A1 - **Recipient organization:** NEW YORK UNIVERSITY - **Principal Investigator:** Jin Kim Montclare - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $545,162 - **Award type:** 1 - **Project period:** 2024-08-01 → 2028-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10979533 ## Citation > US National Institutes of Health, RePORTER application 10979533, Modular Toolbox of Protein and Lipid Hybrid Biomaterials for siRNA Delivery (1R01EB035146-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10979533. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*