# DNA Nanostructures as siRNA Delivery Vehicles for Alzheimer's Therapy

> **NIH NIH R03** · STATE UNIVERSITY OF NEW YORK AT ALBANY · 2022 · $312,417

## Abstract

Project Summary/Abstract
Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, characterized by
progressive deterioration of cognitive capacity. Currently available treatments for AD are symptomatic agents
that aim to improve cognitive and behavioral symptoms without altering the underlying course of the disease or
slowing disease progression. Thus, there is a necessity for disease-modifying treatment strategies for AD that
can block or modify the molecular pathological steps leading to neurodegeneration. RNA interference is one
such strategy that has been actively pursued for selective knockdown of AD target genes, but typically used
viral vectors have preparation and safety concerns.
We propose a new DNA nanotechnology approach to overcome these issues. DNA nanotechnology offers
near-atomic control over building shapes and structures, eliminating heterogeneity in size of drug carriers. DNA
can be functionalized with additional chemical groups that allow controllable attachment of drug molecules and
protect the drug against biological degradation. Since DNA is a biological material, DNA nanostructures elicit
minimal immune response when used in drug delivery, are non-toxic, biocompatible and biodegradable.
Further, DNA nanostructures can enter cells without the need for a transfection agent. Our approach will use
DNA polyhedra as model structures for RNA interference based treatment of AD. Specifically, we will: (1)
develop DNA polyhedra with controllable attachment of small interfering RNAs (siRNAs) and incorporate 2'-O-
methyl strands to enhance biostability in physiological environments, and (2) establish viability of DNA
nanostructure-based drug delivery in human induced pluripotent stem cell (iPSC) derived AD model cell lines.
Our proposal brings together an interdisciplinary team comprising a diverse group of researchers in chemistry,
biology, and neurological disorders to provide a novel approach for RNAi treatment of AD. The proposed
strategy has a number of advantages including (i) precise drug loading and quantification, (i) biocompatibility
and biodegradability, (iii) low dosage with high efficacy, and (iv) enhanced biostability to withstand
physiological conditions and complex biofluids. We anticipate that our approach will provide a robust proof of
concept for viable siRNA delivery by DNA nanostructures with great future potential for clinical treatment of AD.

## Key facts

- **NIH application ID:** 10418236
- **Project number:** 1R03AG076599-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT ALBANY
- **Principal Investigator:** Arun Richard Chandrasekaran
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $312,417
- **Award type:** 1
- **Project period:** 2022-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418236

## Citation

> US National Institutes of Health, RePORTER application 10418236, DNA Nanostructures as siRNA Delivery Vehicles for Alzheimer's Therapy (1R03AG076599-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10418236. Licensed CC0.

---

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