# IL-23 and IL-17A mRNA-targeted oligonucleotide therapeutics in autoimmune uveitis

> **NIH NIH R43** · TARGETSITE THERAPEUTICS CORPORATION · 2021 · $319,794

## Abstract

The pro-inflammatory cytokines IL-23 and IL-17A play critical roles in autoimmune uveitis (AU).
Current AU treatments include immunosuppressants, including systemic corticosteroids,
accompanied by many challenging toxicities. As a novel cytokine gene expression control
mechanism, we found that the microRNA (miRNA) miR466l-3p cooperates with the mRNA-
stabilizing protein HuR to augment IL-17A mRNA and protein levels. To exploit this unusual
miRNA-mediated enhancing mechanism as a potential therapeutic target, TargetSite
Therapeutics and Yale University have collaboratively generated a target site blocker (TSB)
oligonucleotide that specifically blocks miR466l-3p binding to the IL-17A 3’UTR, leading to
transcript decay and decreased IL-17A protein levels both in vitro and in vivo. This includes our
preliminary TSB efficacy data in the rat autoimmune uveitis model. The mRNA levels of IL23, a
cytokine upstream of IL-17A, are also augmented in miR466l-overexpressing cells. This Phase
I SBIR will provide proof-of-concept that miR466l – cytokine mRNA interaction-specific TSB
oligos, either singly or in combination, will be a novel effective treatment for AU. We will do so
by: (1) designing, validating and evaluating specificity of a miR466l – IL-23 3’UTR TSB;
(2) optimizing the IL-17A mRNA-specific TSB for the foundational (rat) model; and (3)
assessing the efficacy of the IL-17A and IL-23 TSBs, singly and in combination, in the rat AU
model, by clinical scoring, histopathology and aqueous humor levels of the TSBs and relevant
cytokines. The achievable milestone for this Phase I SBIR project is >50% reduction in clinical
and histopathologic AU parameters, thereby offering therapeutic benefit of this novel approach
in autoimmune uveitis.

## Key facts

- **NIH application ID:** 10259979
- **Project number:** 1R43EY032840-01
- **Recipient organization:** TARGETSITE THERAPEUTICS CORPORATION
- **Principal Investigator:** Vinod Satisch Ramgolam
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $319,794
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259979

## Citation

> US National Institutes of Health, RePORTER application 10259979, IL-23 and IL-17A mRNA-targeted oligonucleotide therapeutics in autoimmune uveitis (1R43EY032840-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10259979. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*