# Genome engineering therapeutics for cystinuria and its metabolic consequences.

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

ABSTRACT
Cystinuria is an inherited human kidney disease with significant morbidity affecting 1 in 7000, including veterans.
The disease is caused by mutation of genes involved in renal cystine transport resulting in elevated urinary
cystine with kidney stone formation. With the genetic basis of the disorder defined (mutation in SLC3A1,
cystinuria type A), opportunities for targeted molecular therapies exist. Building upon our previous grant, we
propose an innovative experimental design to demonstrate long-term phenotypic correction of cystinuria in an
intact animal using a combination of transposon and adeno-associated virus (AAV) technologies.
In specific aim 1, we will test the ability of hybrid AAV-piggyBac transposon technology to mediate long-term
transgene expression in mouse kidney and correct cystinuria in a Slc3a1-/- mouse model. In specific aim 2, we
will test the ability of novel proximal tubule targeted AAV to deliver transgenes to proximal tubule cells in mice in
vivo. In both aims, we will test delivery to and evaluate for long-term transgene expression in both neonatal and
adult mice. In specific aim 3, we propose to bridge our foundational pre-clinical studies to human application by
testing AAV delivery to human kidney organoids including cystinuria organoids. Our innovative but feasible
studies will expand use of AAV and transposon technology for kidney gene delivery and lay a pre-clinical
foundation for ultimate human therapeutic application for kidney disease in veterans and others.

## Key facts

- **NIH application ID:** 10765675
- **Project number:** 5I01BX004258-06
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** MATTHEW H WILSON
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-04-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765675

## Citation

> US National Institutes of Health, RePORTER application 10765675, Genome engineering therapeutics for cystinuria and its metabolic consequences. (5I01BX004258-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10765675. Licensed CC0.

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