# Development of tools for site-directed analysis of gene function

> **NIH NIH R24** · IOWA STATE UNIVERSITY · 2020 · $62,320

## Abstract

The overarching goal of this application is to create tools and efficient methods to define
genes that can promote human health. While a tremendous amount of data has been cataloged
on gene mutation and changes in gene expression associated with complex human disease,
our understanding of those genes that could be co-opted to restore patient health is lacking. To
address this need and test for genes that when restored to wild type function promote health,
we propose develop mutagenic, revertible and conditional alleles that provide spatial and
temporal control of gene expression. The ability to make site-specific, untagged mutant alleles
in zebrafish and other models has been greatly advanced by custom nucleases that include
TALENs and CRISPR/Cas9 systems. These systems operate on the same principle: they are
designed to bind to specific sequences in the genome and create a double strand break. The
goals of this proposal leverage the activities of TALEN and CRISPR/Cas9 technologies to make
site-specific double strand breaks. These tools and techniques will have direct implications for
providing precise gene editing techniques to assess the roles of genes in disease and their
ability to promote health following disease progression. While we will develop these
methodologies in zebrafish due to their ease of gene delivery, we anticipate these
methodologies will not only enhance the efficiency of gene editing but will be readily adaptable
for use in other model organisms and large animals. In our opinion, this will have important
implications for modeling human disease and health in animal systems by greatly enhancing the
ability to make predictable alleles, small nucleotide polymorphisms similar to those associated
with human disease, and conditional alleles to test for the ability of a gene to restore health.

## Key facts

- **NIH application ID:** 10187374
- **Project number:** 3R24OD020166-05S2
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** KARL J CLARK
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $62,320
- **Award type:** 3
- **Project period:** 2020-08-15 → 2021-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187374

## Citation

> US National Institutes of Health, RePORTER application 10187374, Development of tools for site-directed analysis of gene function (3R24OD020166-05S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10187374. Licensed CC0.

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