# Development of DNA-linked Matrix Metallo Protease activity probes in Osteoarthritis research

> **NIH NIH R43** · DENCODA LLC · 2022 · $256,586

## Abstract

Project summary
Currently, more than 32 million American suffer from osteoarthritis (OA), which incurred healthcare costs of
~$5 billion in FY2019. These costs are high largely because physicians lack early diagnosis capabilities that
would permit the prescription of preventative therapies to at-risk individuals. In addition, no consensus
biomarker exists for OA diagnosis due to the lack of validation and poor quantification, which impedes OA
pharmaceutical development. Therefore, there is an unmet need for new clinical and research tools for OA.
Active matrix-metalloproteases (MMPs) play significant roles in the pathogenesis of OA by degrading extracellular
matrix components. High levels of certain MMPs were observed in the synovial fluid of OA patients. The early
detection of elevated MMPs may be of clinical benefit as it would permit the earlier implementation of therapeutic
regimens capable of delaying or preventing disease progression. These MMPs belong to a family of zinc-
dependent proteases implicated in numerous disease types, such as cancers, cardiovascular disease, arthritis,
and autoimmune diseases. Current methods used by researchers and clinicians to monitor MMP activities lack
many desirable features such as specificity, sensitivity, and accuracy. The goal of this Phase I study is to
address unmet clinical needs by developing a highly sensitive, selective, and multiplexed MMP activity assay
using Dencoda’s proprietary and innovative DNA-based activity detection system using OA as a model system.
The use of nucleic acid-based technologies in laboratory and clinical assays is well-known and well-proven in
most the recent COVID-19 outbreak. Our activity assay uses MMP active site probes to encode the activities of
target MMPs into DNA. As such, our platform realized multiple advantages over current assays, such as
reporting on the specific MMP activities as opposed to levels alone, cost effectiveness, high throughput,
multiplexing format, and high sensitivity. In Aim 1, we will develop and validate multiplexing DNA-linked MMP
activity probes specific to MMP-1 and -9. Synovial fluid from OA patients will be used for this validation. In Aim
2, we will further reduce the cost of our proprietary assay system. Currently, our platform requires antibodies
specific to each individual MMP. We will aim to reduce costs via the selection of MMP-1 and -9-specific binding
molecules using in vitro selection methods, namely, mRNA display and DNA aptamer selection. Overall, the
key metrics for success for this Phase I study will be the demonstration and validation of the assay specificity
with a dynamic range of 5-log10 scale compared to negative controls. The successful outcome of these studies
will validate the feasibility of our innovative assay format for specific MMP activity detection. Ultimately, our
novel DNA-based MMP activity assay platform will address the limitations facing OA diagnosis and
pharmaceutical development by lowering healthcare...

## Key facts

- **NIH application ID:** 10479317
- **Project number:** 1R43AR079941-01A1
- **Recipient organization:** DENCODA LLC
- **Principal Investigator:** Dongwook Kim
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $256,586
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10479317

## Citation

> US National Institutes of Health, RePORTER application 10479317, Development of DNA-linked Matrix Metallo Protease activity probes in Osteoarthritis research (1R43AR079941-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10479317. Licensed CC0.

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