# CLAP-seq: An Aptamer-Based Platform for Transcriptome-Wide Mapping of RNA Modifications

> **NIH NIH R21** · TEXAS A&M UNIVERSITY · 2020 · $216,525

## Abstract

Project Summary/Abstract
Beginning in the 1950s, more than 100 types of posttranscriptional modifications have been identified in
cellular RNA. Today, the study of RNA post-transcriptional modifications – known as epitranscriptomics – is a
rapidly developing field, which promises to greatly enhance our understanding of human health and disease.
Despite the profound implications already assigned to many RNA modifications, their precise functions remain
poorly understood. This can be attributed to the lack of sensitive and robust sequencing technologies to detect
these epitranscriptomics marks in a transcriptome-wide manner. A key bottleneck is the lack of sensitive and
specific enrichment techniques (affinity- or reactivity-based) for RNA molecules containing these modifications.
The proposed research takes direct aim at this critical deficit using the aptamer approach, employing in vitro
selection methods to identify nucleic acid molecules that bind chemically modified RNAs. These aptamers are
unique in that they are comprised of L-(deoxy)ribose-based nucleic acids (L-DNA and L-RNA), which are mirror
images (enantiomers) of natural D-nucleotides. L-Aptamers, which are completely orthogonal to natural biology,
are extremely well suited for binding RNA targets. Therefore, in vitro selection will be used to isolate novel L-
aptamers capable of binding chemically modified mononucleotides, which will enable selective capture of RNA
molecules containing the same modified residue. These L-aptamers will then be used in Cross-Linking-
Aptamer Pull-down and sequencing (CLAP-seq), the first transcriptome-wide profiling technology employing
aptamer-based RNA enrichment prior to next-generation sequencing. CLAP-seq not only promises to open a
general and robust route towards transcriptome-wide profiling of the growing list of RNA modifications, but also
promises to reinforce our current view of the epitranscriptome. Accordingly, the development of CLAP-seq will
have a profound impact on the field of epitranscriptomics, which is well aligned with the mission of the NICHD
and the goal of this FOA: to promote research into the role of RNA chemical modifications in development and
related disease.

## Key facts

- **NIH application ID:** 9988492
- **Project number:** 5R21HD099707-02
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Jonathan Thomas Sczepanski
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $216,525
- **Award type:** 5
- **Project period:** 2019-08-02 → 2022-08-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988492

## Citation

> US National Institutes of Health, RePORTER application 9988492, CLAP-seq: An Aptamer-Based Platform for Transcriptome-Wide Mapping of RNA Modifications (5R21HD099707-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9988492. Licensed CC0.

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