# IL-17A mRNA-targeted oligonucleotide therapeutics in Idiopathic Pulmonary Fibrosis (IPF)

> **NIH NIH R43** · TARGETSITE THERAPEUTICS CORPORATION · 2023 · $245,000

## Abstract

Abstract. Idiopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disorder affecting ∼3 million
people worldwide with function-limiting progressive symptoms and a 2-3 year median survival time from
diagnosis. While the etiology of IPF is not clear, genetic factors, environmental exposures and microbial
pathogens have been identified as IPF risk factors. Pirfenidone and nintedanib currently are two orally
administrated fibrosis inhibitors. However, both are accompanied by a wide adverse effect profile, limiting utility.
Thus, a high unmet need exists for tolerable and effective treatment options. Based on a discovery in the
academic partner Yale university laboratory, TargetSite Therapeutics Corporation is developing a novel class of
oligonucleotide therapeutic agents that selectively interfere with the binding interaction of an “enhancing
microRNA” (e-miRNA), miR466l-3p, to specific target sites within an mRNA’s 3’UTR. These “target site blocking”
(TSB) oligonucleotides effectively and specifically interfere with the production of individual pro-inflammatory
cytokines and growth factors including IL-17A, IL-22, GM-CSF, IL-23A, VEGF-A and IL-1β. IL-17A has been
reported to be significantly elevated in the bronchoalveolar lavage (BAL) fluid of IPF patients. We therefore
propose targeting the IL-17A mRNA with a specific TSB and assess its efficacy in the established bleomycin-
induced lung fibrosis (IPF) model. In partnership with Matinas Biopharma, attempts will be made to encapsulate
the IL-17A TSB in multilayered lipid nanocrystals, which are optimized for oral delivery. We will validate the
efficacy of these TSB-LNC in Th17 cells in vitro, and for their biological activity in reduction of LPS-induced IL-
17A in mice. The efficacy of LNC-encapsulated and naked (PBS) IL-17A TSB oligos will be tested, both by
intraperitoneal and oral (via gavage) delivery, in the bleomycin-induced murine IPF model. Primary assessment
parameters will be lung fibrosis, histopathological and biochemically, as well as BAL fluid and serum IL-17A
levels. A reduction in disease severity, as determined by >50% reduction in quantifiable fibrosis, is expected as
an achievable milestone and a definable criterion for success. Experimental evidence from this project will
confirm whether the IL-17 mRNA-directed oligos beneficially modify the disease, providing a novel therapeutic
in the treatment of IPF.

## Key facts

- **NIH application ID:** 10761365
- **Project number:** 1R43HL170910-01
- **Recipient organization:** TARGETSITE THERAPEUTICS CORPORATION
- **Principal Investigator:** JEFFREY R. BENDER
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $245,000
- **Award type:** 1
- **Project period:** 2023-08-18 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10761365

## Citation

> US National Institutes of Health, RePORTER application 10761365, IL-17A mRNA-targeted oligonucleotide therapeutics in Idiopathic Pulmonary Fibrosis (IPF) (1R43HL170910-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10761365. Licensed CC0.

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