# The impact of RNA chemical modifications on polycystic kidney disease progression

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $427,879

## Abstract

Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is amongst the most common monogenetic
human disorders. Nearly 600,000 Americans are affected by this devastating condition.
Unfortunately, treatment options are limited. To address this large unmet need, we will explore a
novel therapeutic opportunity involving targeting the RNA chemical modification pathway. It has now
become clear that, like DNA, RNA also undergoes dynamic chemical changes that impacts its
processing and function. In preliminary analysis we found that mRNAs from cystic kidneys exhibit
higher levels of a specific RNA modification called m6A, which refers to methylation of the 6th
nitrogen in adenosine. Moreover, we noted that reducing m6A levels by deleting Mettl3, a key
enzyme that mediates this modification, ameliorates preclinical PKD. Further mechanistic studies
suggested a novel hypothesis that lowering m6A levels alleviates PKD by reducing translation of
pathogenic mRNAs. Based on these promising observations, we propose to: (a) use complementary
genetic and pharmaceutical approaches to conclusively validate the Mettl3/m6A pathway as new
drug target in ADPKD. (b) Identify the m6A-regulated pathogenic proteome in ADPKD. In summary,
RNA modification is an emerging field with broad implications in physiology and disease, yet its
impact on kidneys is unknown. We are the first to address these fundamental knowledge gaps.
Building on our strengths in RNA and ASO biology, we will also uncover a novel drug target for
ADPKD.

## Key facts

- **NIH application ID:** 10356850
- **Project number:** 5R01DK102572-07
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Vishal Patel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $427,879
- **Award type:** 5
- **Project period:** 2015-05-11 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356850

## Citation

> US National Institutes of Health, RePORTER application 10356850, The impact of RNA chemical modifications on polycystic kidney disease progression (5R01DK102572-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10356850. Licensed CC0.

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