# Localized SDF-1 mRNA nanoparticle delivery for treating erectile dysfunction. > **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $477,766 ## Abstract PROJECT SUMMARY About 18 million men in the U.S. are affected by erectile dysfunction (ED), and it is estimated to affect 322 million men worldwide by 2025. ED is caused by various conditions that perturb vascular, nervous and/or hormonal systems, imposing profound negative impacts on quality of life and well-being of affected males. Advent of oral formulations of phosphodiesterase type 5 inhibitors (e.g., Viagra®) has provided a breakthrough in managing ED to a certain degree but are frequently ineffective due to underlying neurovascular dysfunction, and often accompanies systemic side effects and undesired drug-drug interactions. To this end, a therapeutic modality that can intervene the natural histology of the disease among a broader affected population is sorely needed. We have recently discovered that human recombinant stromal cell-derived factor-1 (SDF-1) promotes regeneration of penile vasculatures, nerves and muscles to restore erectile function in a rat model of ED. The improvement was associated with increases in major pelvic ganglion neurons and growth factor expression, upregulation of stem-cell associated genes and decrease in penile fibrosis. Importantly, SDF-1 targets a broad array of repair mechanisms by acting directly on resident tissues and activating stem-cell associated repair pathways to enhance the integrity of tissue architecture and functional response. However, protein-based therapy requires multiple and frequent doses to meet the required therapeutic window, leading to economic and compliance issues. This is of particular concern for SDF-1 due to its very short half-live, measured in minutes. We thus propose here to develop mRNA-based SDF-1 therapy, with a particular focus on designing nanoparticle-based platforms providing safety and efficient mRNA delivery to penile cells, for sustainable ED treatment. Our interest lies in nanoparticles based on environmentally-sensitive cationic polymers that gradually degrade in physiological environments to facilitate mRNA release, ideally in intracellular milieu, and removal of carrier materials from body. Encouragingly, our pilot data demonstrates that at least four nanoparticles based on our custom-synthesized polymers provide significantly enhanced reporter mRNA expression in rodent penile tissues in vivo compared to a gold-standard polymeric delivery system. We note that chemical variations of these polymers can further improve mRNA delivery characteristics, such as broader tissue coverage and/or enhanced transfection efficiency. To this end, we will synthesize a panel of chemically- distinct environmentally-sensitive polymers and extensive screen in vitro and in vivo to determine lead candidates that provide highly efficiently and safe penile mRNA expression. The lead candidates will then be used to package and deliver optimized SDF-1 mRNA into the injured penile tissues of a rat model of ED to establish clinical relevance. Successful execution of the proposed studies would ... ## Key facts - **NIH application ID:** 10422778 - **Project number:** 1R01DK132425-01 - **Recipient organization:** JOHNS HOPKINS UNIVERSITY - **Principal Investigator:** Johanna Lucy Hannan - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $477,766 - **Award type:** 1 - **Project period:** 2022-05-01 → 2026-04-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10422778 ## Citation > US National Institutes of Health, RePORTER application 10422778, Localized SDF-1 mRNA nanoparticle delivery for treating erectile dysfunction. (1R01DK132425-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10422778. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*