# In vivo selection of gene modified hepatocytes

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $495,054

## Abstract

Today the clinical application of many otherwise promising new strategies for liver directed gene and cell
therapy is hampered by their inherent quantitative inefficiency. Here we propose to use in vivo selection to
overcome these problems. We will develop clinically applicable ways to use small molecule drugs to select
genetically modified hepatocytes in vivo and thereby cross the quantitative threshold required for permanent
therapeutic benefit. We have identified the fever medication acetaminophen (APAP) as excellent candidate for
this approach.
Three specific aims are designed to fully validate these novel method for in vivo selection of therapeutically
modified hepatocytes.
In Aim 1, we will develop integrating rAAV vectors (Generide vectors) that can be selected by APAP and in aim
2,conditionally selectable lentiviral vectors will be generated. Both will be validated in metabolic disease
models. In Aim 3, we will apply the results of Aims 1&2 to human hepatocytes. Selection of genetically
modified human hepatocytes will be carried out in liver chimeric mice.

## Key facts

- **NIH application ID:** 10378002
- **Project number:** 5R01DK123093-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Markus Grompe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $495,054
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378002

## Citation

> US National Institutes of Health, RePORTER application 10378002, In vivo selection of gene modified hepatocytes (5R01DK123093-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10378002. Licensed CC0.

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