# Machine learning-enabled Comparative Transcriptomic Profiling to Validate NanoScript-induced Inner Ear Hair Cells

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2021 · $311,115

## Abstract

PROJECT SUMMARY
 Hearing loss during early childhood significantly affects learning and acquisition of social skills, while hearing
loss in adults can often result in social isolation and the inability to perform many routine social functions. A
leading cause of sensorineural hearing loss is the loss of sensory hair cells of the inner ear. A lifetime exposure
to aminoglycoside and loud sounds will result in an estimated 15% of adult Americans (~36 million) having some
form of hearing loss. A promising approach to mitigate hearing loss and deafness is a cell replacement therapy
by transdifferentiating supporting cells into hair cells. Unfortunately, current approaches for transdifferentiation
rely on viral delivery may be unsafe and impractical for clinical translation. Therefore, there is a critical need to
develop alternative platforms for regulating gene expression and inducing transdifferentiation in an efficient, non-
viral manner that is suitable for restoration of hearing.
 To this end, our long-term goal is to develop NanoScript, an innovative, tunable nanoparticle-based artificial
transcription factor platform capable of effectively regulating gene expression in a non-viral manner. Using
NanoScript, we will transdifferentiate supporting cells into functional hair cells. NanoScript consists of a
nanoparticle functionalized with specific small molecules and peptides that are designed to mimic the individual
domains of natural transcription factor (TF) proteins. TFs are endogenous, multi-domain proteins that orchestrate
many cellular functions, including differentiation. Since NanoScript is a functional replica of TF proteins, it can
replace virally-delivered TFs for regenerative medicine-based applications. The overall objective of this proposal
is to design three NanoScripts that mimic three TFs essential for hair cell differentiation (Gfi1, Pou4f3, and Atoh1;
GPA). We will test whether GPA-NanoScript binds to the same DNA sequence and activate gene expression in
vitro. Next, we will determine if the addition of epigenetic modulators to GPA-NanoScript will bind to the same
targets as the TF proteins, locally alter the chromatin structure and enhance gene expression. Finally, we will
use cochlear explants to determine whether GPA-NanoScript promotes transdifferentiation of supporting cells
into hair cells by single-cell transcriptome analysis. Generation of nascent hair cells using an ex vivo model will
serve as a springboard to test NanoScript technology for regenerative medicine. It will also establish NanoScript
as an effective and non-viral tool for researchers to generate functional cells via direct reprogramming.

## Key facts

- **NIH application ID:** 10412274
- **Project number:** 3R01DC016612-04S2
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Kelvin Y. Kwan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $311,115
- **Award type:** 3
- **Project period:** 2018-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412274

## Citation

> US National Institutes of Health, RePORTER application 10412274, Machine learning-enabled Comparative Transcriptomic Profiling to Validate NanoScript-induced Inner Ear Hair Cells (3R01DC016612-04S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10412274. Licensed CC0.

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