# Chemically Assisted Electrotransfer of DNA

> **NIH NIH R35** · DUKE UNIVERSITY · 2022 · $402,500

## Abstract

Abstract
Electrotransfer (ET) or electroporation has been widely used to deliver molecular cargo into cells for genome
and epigenome editing, cell engineering, and DNA vaccination in treatment and prevention of diseases (e.g., the
COVID-19 pandemic). To enhance ET efficiency, different chemicals have been combined with electric pulses
in treatment of cells. However, a challenge with this strategy is how to screen for chemicals. In most studies, the
screening process is accomplished empirically in vitro, but this approach is impractical or prohibitive in vivo.
Furthermore, a chemical treatment that works well for ET in cultured cells may not necessarily work for ET in the
body. To this end, the proposed study will explore a new approach to chemical screening. Since mechanisms
governing molecular transport are conserved across different cells and tissues, can chemical treatments that
assist DNA transport be used to ubiquitously improve ET in vitro and in vivo?
To answer this question, the Yuan lab will build upon their previous successes to deepen the understanding of
transport mechanisms. One area of focus is to investigate cytoplasmic transport. Specifically, the study will
determine mechanisms of vesicular transport and the escape of DNA from vesicles prior to nuclear entry. The
second area of focus is to investigate the nuclear entry of DNA in non-dividing cells. The study will address key
questions such as: How does DNA travel through the nuclear pore complex? How does the transport depend on
the size and structures of DNA? How does the amount of nuclear localization signal or DNA nuclear targeting
sequence per DNA molecule influence the transport? In addition to the mechanistic studies, the Yuan lab will
develop new techniques to screen for nontoxic compounds and nanoparticles that can be used to improve
cytoplasmic transport and nuclear entry. The third area of focus is to explore different combinations of strategies
to simultaneously improve intracellular and extracellular transport of DNA in tissues. The study will demonstrate
that the combination can synergistically enhance ET efficiency and prolong the transgene expression in vivo.
The Yuan lab has extensive experiences in the analysis of molecular transport in cells and tissues, especially in
the context of ET research. This R35 will give the lab the flexibility and power to advance the understanding of
transport mechanisms, and open new avenues for research and applications. Findings from the studies
mentioned above will lead to the development of common strategies to enhance DNA transport that in turn will
improve ET in vitro and in vivo.

## Key facts

- **NIH application ID:** 10406467
- **Project number:** 1R35GM145362-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** FAN YUAN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,500
- **Award type:** 1
- **Project period:** 2022-09-21 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406467

## Citation

> US National Institutes of Health, RePORTER application 10406467, Chemically Assisted Electrotransfer of DNA (1R35GM145362-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10406467. Licensed CC0.

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