# Targeted delivery of novel miRNA-based therapeutics for pneumonia-induced acute lung injury

> **NIH NIH R41** · ADVAC THERAPEUTIC, LLC · 2022 · $296,926

## Abstract

SUMMARY
We propose to develop a novel miRNA-based therapeutic to treat acute lung injury in a bacterial pneumonia
model. Bacterial pneumonia is a leading cause of serious and lethal infections in children and the elderly
worldwide. Even with antibiotic intervention, many patients still rapidly progress to acute respiratory distress
syndrome (ARDS) requiring hospitalization, intensive care, and mechanical ventilation. Mortality rate in ARDS
patients is high, with many survivors still facing a long road to recovery from various long-term complications of
lung dysfunction. Recovery from ARDS is critically dependent on regeneration of the damaged airway epithelial
cells, and failure to repair epithelial damage impairs lung function and leaves airways vulnerable to recurrent
infection and airway inflammation. There are currently no FDA approved therapies to stimulate regrowth of
lung tissue to repair lung injury, which would provide great benefits to pneumonia/ARDS patients. In our
preliminary studies using a mouse model of pneumonia caused by Streptococcus pneumoniae (Sp), we
observed acute lung injury with substantial destruction of airway epithelial cells (AECs) and extensive damage
to the distal airway of the parenchyma, similar to pathology described in human patients with ARDS. We
discovered that Sp-infection induces lung expression in the lung of a specific family of miRNA that plays a
critical role in the generation of respiratory epithelia during embryogenesis. To test the role of this miRNA in
repairing lung injury, we treated Sp-infected mice with liposomes loaded with “miRNA-mimic”, a double-
stranded RNA molecule intended to mimic and augment the function of endogenous miRNA in vivo. We found
that administration of miRNA-mimic to Sp-infected mice promoted airway epithelial regeneration, resulting in
improved lung function, enhanced host recovery and survival. To translate these findings into clinical
application, we propose to further improve this technology with targeted delivery of miRNA-mimic to inflamed
lungs, to increase efficacy, minimize off-target effects, and reduce potential drug toxicity. To this end, we will
develop alveolar-targeted liposomes (ATLs) loaded with miRNA-mimic and assess lung accumulation and
therapeutic efficacy after intravenous administration compared to the non-targeted counterparts. We will also
evaluate pharmacokinetics/bio-distribution/pharmacodynamics and safety profiles in Sp-infected mice and ex
vivo human lung. The results of this phase I STTR project will set the stage for future studies to develop a first-
in-class drug of regenerative medicine for treating pneumonia/ARDS.

## Key facts

- **NIH application ID:** 10395376
- **Project number:** 1R41AI155327-01A1
- **Recipient organization:** ADVAC THERAPEUTIC, LLC
- **Principal Investigator:** Brian Akerley
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $296,926
- **Award type:** 1
- **Project period:** 2022-09-08 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395376

## Citation

> US National Institutes of Health, RePORTER application 10395376, Targeted delivery of novel miRNA-based therapeutics for pneumonia-induced acute lung injury (1R41AI155327-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10395376. Licensed CC0.

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