# Facilitating Endogenous Bone Repair in Arthritis with Targeted IL-27 Sonodelivery

> **NIH NIH R01** · PURDUE UNIVERSITY · 2022 · $335,126

## Abstract

PROJECT SUMMARY
 Improved control over synovial inflammation is anticiapted to slow bone erosion and reduce the risk of
fractures and pain. However, even potent anti-inflammatory strategies such as blockade of TNF or IL6R, only
show limited bone repair, suggesting that suppressing inflammation is insufficient to restore osteo-immune
balance. Some current and emerging therapies succeed in slowing erosion by suppressing osteoclast activity,
but fail to significantly stimulate bone formation. Further, these biologics are not targeted for accumulation at
inflammed joints, thus are administered systemically, enhancing the likelihood of serious infection. For
therapeutics to succeed in promoting bone repair, they likely must balance levels and activity of several
proinflammatory cells to disrupt their interaction with osteoclasts, and promote osteoblast maturation or activity.
Thus a critical unmet need for inflammatory bone loss is an intervention that can restore eroded bone through
rebalancing immune:bone cell homeostasis in order to reduce fracture risk and improve quality of life for
patients. Recent data points to a novel use for cytokine Interleukin-27 (IL-27) as a regulator of immune and
bone cell balance, as it reduces osteoclastogenesis and promotes osteoblast proliferation and maturation.
Also, IL-27 suppresses activities of immune and synovial cells mediating the onset and maintenance of
inflammation and also has anti-angiogenic activity. Current strategies for delivering recombinant (r)IL-27 are
systemic and lack specificity to immune or bone cells, and moreover are unable to sustain therapeutic effects
over time due to rapid clearance. We propose to examine whether a targeted IL-27, delivered using a
sustained expression system, will be effective in promoting bone repair and reducing inflammation in joints
using a collagen-antibody induced arthritis (CAIA) model. Intraarticular sonoporation gene delivery
(sonodelivery) will transfer into the joints a nanoplex of polymer and plasmid DNA encoding targeted IL-27 to
reduce inflammation and promote bone repair. Our hypothesis is that optimizing delivery and targeting of IL-27
to joints will facilitate endogenous bone repair by re-balancing osteo-immune homeostasis.
 To test this hypothesis, we propose 1) To achieve therapeutic levels of cytokine in joints, we will optimize
IL-27 intra-articular sonodelivery; 2) To enhance cytokine retention in bone and promote endogenous bone
repair, we will promote ligand-mediated targeting of IL-27 to bone cells or matrix, and 3) To enhance cytokine
retention at the pannus and synovial lining and facilitate bone repair, we will promote ligand-mediated targeting
of IL-27 to inflammatory and immune cells. We anticipate that this simple sonodelivery strategy will provide an
efficient means to restore eroded bone in articulations affected by rheumatoid arthritis (RA). IL-27 is unique in
its ability to simultaneously inhibit inflammation and promote bone repair. ...

## Key facts

- **NIH application ID:** 10352199
- **Project number:** 5R01AR069079-05
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Marxa L Figueiredo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $335,126
- **Award type:** 5
- **Project period:** 2018-02-16 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352199

## Citation

> US National Institutes of Health, RePORTER application 10352199, Facilitating Endogenous Bone Repair in Arthritis with Targeted IL-27 Sonodelivery (5R01AR069079-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10352199. Licensed CC0.

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