# Viral Tool Development Core: Visualization and manipulation of brain fluid dynamics by recombinant viral vectors

> **NIH NIH U19** · UNIVERSITY OF ROCHESTER · 2022 · $150,923

## Abstract

Viral Tool Development Core - Abstract
Expression of genetically encoded biosensors and cell-type-specific opto-/pharmacogenetic manipulation
represent effective approaches to reveal the mechanisms behind brain fluid dynamics during sleep. Most current
technologies for labeling brain circulation are invasive and alter dynamics of cerebrospinal fluid (CSF) flow. The
Viral Tool Development Core will develop novel, minimally-invasive methods to transform the study of CSF flow.
The Core will support Projects 2 and 3 by providing viral vectors designed to label key fluid compartments,
specifically interstitial fluid, CSF, and blood. This will be achieved by a combination of capsids, promoters, signal
peptides, and gene traps in the case of adeno-associated viral vector (AAV). Other recombinant viral vectors will
be designed as needed. In Aim 1, we will swiftly establish a viral tool development pipeline to provide in vivo
verified viral vectors that will be optimized and validated. In Aim 2, we will engineer a set of viral tools that will
express fluorescent albumin by transfecting the liver, allowing longitudinal vascular imaging after a single
intravenous injection. In Aim 3, we will extend the utility of the blood probe by attaching biosensors or photo-
activatable fluorescent proteins to report blood conditions or visualize CSF. In Aim 4, we will engineer a knock-
in AAV vector to incorporate successful probes for permanent expression.
 The virally mediated expression of the innovative probes will allow for longitudinal imaging in existing
transgenic mice without a need for further breeding, hence provides cost- and time-effective solutions for this
research program. While the core will closely interact with Projects 2 and 3, the in vivo testing results for novel
viral vectors will be shared and analyzed with the Data Science Core for comparisons with conventional probes.
New probe ideas will be discussed with all research teams to determine the critical measurements that optical
imaging can provide particularly from theoretical (Project 1) and human brain (Project 4) viewpoints.

## Key facts

- **NIH application ID:** 10516500
- **Project number:** 1U19NS128613-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Hajime Hirase
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $150,923
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10516500

## Citation

> US National Institutes of Health, RePORTER application 10516500, Viral Tool Development Core: Visualization and manipulation of brain fluid dynamics by recombinant viral vectors (1U19NS128613-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10516500. Licensed CC0.

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