# Noninvasive site-specific measurement of gene expression in deep tissues with secreted reporters

> **NIH NIH R21** · RICE UNIVERSITY · 2022 · $220,176

## Abstract

Project Summary
Monitoring gene delivery in deep tissues is critical for in vivo studies and translation of gene therapies, but
available methods for achieving such measurements have limited capabilities. Ideally, levels of gene expression
could be noninvasively measured anywhere in the body of both small and large animals. Ideally, multiple genes
could be measured at once, without the need for expensive equipment that would put such a method out of
financial reach for academic research groups. However, no such method exists as of now. In this proposal, we
will develop technologies for monitoring gene expression that, when fully developed, will be: 1) noninvasive, 2)
site-specific, 3) could view multiple types of molecules at once (high-multiplexity of imaging), 4) are not impacted
by the depth of penetration, skull thickness, or organ size; 5) will use inexpensive equipment allowing
democratized access. To achieve this, we will attempt a drastically different approach – instead of imaging
reporters within the deep tissue, we will design reporters that can be easily transported from a known region of
the brain into the blood, where they can be easily measured. We will develop two independent methods for
achieving this goal. First, will express gene expression reporters that exit the cells into brain interstitial space.
Then we will temporarily enhance vascular permeability in selected ~millimeter-sized brain regions to allow for
free diffusion of these reporters from the brain into the blood. In the second method, we will develop a new class
of gene expression reporters that can cross through an intact brain vasculature to continuously report on gene
expression within the transduced brain cells. Spatial precision could be provided for this method using
noninvasive gene delivery that genetically labels cells with site-specificity. With each of these methods, we will
be able to measure gene expression in a specific brain region with a simple blood draw. Our technologies will
be particularly beneficial in the studies of large animal species, where monitoring gene expression in the brain,
in most cases, is not feasible without euthanasia. While initially focused on the brain as a test-case with a high
need for such methods, the same concepts can be applied to other tissues.

## Key facts

- **NIH application ID:** 10432370
- **Project number:** 1R21EB033059-01
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Jerzy Olgierd Szablowski
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $220,176
- **Award type:** 1
- **Project period:** 2022-09-13 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10432370

## Citation

> US National Institutes of Health, RePORTER application 10432370, Noninvasive site-specific measurement of gene expression in deep tissues with secreted reporters (1R21EB033059-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10432370. Licensed CC0.

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