# Improving biological nanopores for precision nucleic acid sequencing using a computational microscope

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $266,532

## Abstract

This project aims to develop a tool that can considerably increase the precision of nucleic acid
sequencing by enabling rational engineering of biological nanopores for sequencing applications.
Although the methodology of nanopore sequencing has undergone major improvement with
regard to transporting DNA and RNA molecules through the nanopore, sample preparation, base-
calling algorithms, etc., relatively little has been published on improving the raw accuracy of
nucleotide detection, which is the most commonly quoted deficiency of the nanopore sequencing
method. This project will address this deficiency by developing a computational technology that
will greatly simplify the design of custom nanopores for RNA and DNA sequencing, potentially
leading to orders-of-magnitude improvement in row read accuracy. The key innovation of the
project exploits recent methodological advances that have made plausible de novo prediction of
nanopore current levels from simulations alone. To transform this methodological breakthrough
into an accurate nanopore design tool, this project will examine and improve the simulation
methodology guided by a set of experiments designed specifically to provide the information
needed to improve the model. The practical utility of the method will be demonstrated by designing
custom pores to detect biologically significant RNA modifications. The resulting computational
method will be made available to the research community in the form of self-contained and well-
documented software. This project will be realized by an interdisciplinary team that combines
expertise in biological (UMass) nanopore experiment with theoretical and computation modeling
(UIUC).The two PIs involved each have over 15 years of experience with research on nanopore
technology, which includes synthesis and characterization of biological nanopores (Chen) and
microscopic simulations of DNA and ion transport through biological nanopores (Aksimentiev).

## Key facts

- **NIH application ID:** 10414906
- **Project number:** 5R21HG011741-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Aleksei Aksimentiev
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $266,532
- **Award type:** 5
- **Project period:** 2021-06-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414906

## Citation

> US National Institutes of Health, RePORTER application 10414906, Improving biological nanopores for precision nucleic acid sequencing using a computational microscope (5R21HG011741-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10414906. Licensed CC0.

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