# Catalytic Nanotherapies to Treat Lung Disease

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $382,560

## Abstract

Asthma is characterized by airway hyper-responsiveness, inflammation, and dysregulation of innate and
adaptive immunity. Interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) are characteristic
cytokines upregulated in the type 2 helper T cell (Th2) endotype which is the most common form of asthma
Expression of these cytokines is driven, in part, by the zinc-finger transcriptional activator, GATA3, which is
expressed in different lung cells, such as mast cells, macrophages, and epithelial cells. Indeed, targeting
GATA3 is a promising therapeutic avenue to treat asthmatic patients with the Th2 endotype. Several methods
to block GATA3 expression levels by knockdown have been previously investigated, including antisense,
siRNA, and DNA enzyme (Dz) based approaches. Among these gene-regulation strategies, Dz-based
targeting of GATA3 has shown the greatest promise having passed phase II human trials as a treatment for
moderate asthma. The efficacy of Dzs is due to the fact that these molecules are short DNA oligonucleotide
that catalytically degrades target mRNA, and thus are more efficient compared to antisense and avoiding the
immunogenicity and stability issues of RNAi. Through a highly interdisciplinary collaboration between Dr.
Salaita (co-PI) and Dr. Wongtrakool (co-PI), the team has obtained preliminary data showing that GATA3-
cleaving DNAzyme nanoparticles (DzNP) are 100-fold more active at cleaving GATA-3 compared to soluble
Dzs. Importantly, DzNPs also demonstrate significant efficacy in a Th2 mouse model of asthma. The goal of
this proposal is to determine why DzNPs mediate improved efficacy compared to soluble Dzs by elucidating
the mechanism of how GATA3-DzNPs differ from Dzs in terms of internalization, cell targeting, and stability.
Our premise is that DzNPs are more effective compared to soluble Dzs due to the selective delivery of their
payload in scavenger receptor expressing cells, which are upregulated in the Th2 endotype. The long-term
goal of this proposal is to pave the way for the rational design of improved treatments of lung disease.

## Key facts

- **NIH application ID:** 9977246
- **Project number:** 5R01HL142866-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Khalid S. Salaita
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,560
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977246

## Citation

> US National Institutes of Health, RePORTER application 9977246, Catalytic Nanotherapies to Treat Lung Disease (5R01HL142866-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977246. Licensed CC0.

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