# 8-Oxo-7,8-dihydroguanosine in aptamer development and its impact on RNA structure

> **NIH NIH R15** · UNIVERSITY OF COLORADO DENVER · 2023 · $458,356

## Abstract

Project Summary:
 Aptamers have become important tools with a wide variety of applications, including in diagnostics, as
therapeutics, biological reporters, or materials, among others. However, their use has been limited to the four
canonical nucleobases (A, G, C, U), with seldom exceptions. The Resendiz lab was the first one to show that
8-oxo-7,8-dihydroguanosine (8-oxoG) can be used as a building block to obtain aptamers of RNA with
increased or altered specificity towards their cognate target(s). Thus, effectively increasing the aptamer's
chemical space to recognize new targets. The proposed work will exploit this breakthrough to 1) design
oxidized RNA conjugate aptamers (ORCAs) bound to a solid support, for their use to select metabolites of
potential interest; 2) establish the impact that 8-oxoG has on three structural motifs (hairpins, loop bulges,
internal loops) that play important roles in recognition; and 3) introduce chemical modifications that ensure the
chemical and enzymatic stability of the ORCAs, while probing that recognition is not diminished or lost.
 Expanding the aptamer `toolkit' will increase their potential as important biological tools; furthermore,
 understanding how this modification impacts the structure of RNA has broader biological implications.
 8-OxoG is a chemical modification that can be generated, within biological systems, under oxidative
stress. The PI's group has shown that its presence within strands of RNA can alter its reactivity towards
ribonucleases and other enzymes due, in part, to its ability to undergo conformational changes that expose
distinct H-bonding patterns. While this is generally viewed as `unwanted' in nature, the PI's groups uses this
property to control the affinity and specificity of aptamers. Aim 1 has the potential to yield technology that can
be used in detection/diagnostics and, eventually, in treatment. Aim 2 will yield important information that aids
in the rational design of aptamers containing 8-oxoG; while shedding light on the impact that 8-oxoG has on
RNA structure and function, a topic of wide interest due to the presence of this oxidative lesion in living
organisms, and the lack of knowledge in this regard. Aim 3 will focus on preparing aptamers that are
chemically and enzymatically stable; where the synthesis will be developed and expected to be of interest to
the scientific community, broadly.
 The proposed research has the potential to be of high impact, and of interest to various fields.
Importantly, its interdisciplinary nature will attract students with various professional interests, and will serve as
guide and foundation to ensure a successful transition onto their next academic/professional step. A
consequence of these efforts will be the strengthening of the PI's research program, department, and CU
Denver as a whole. Shaping/reinforcing the interest of students in the biomedical field, from an early stage,
while providing high quality training, will ensure that a...

## Key facts

- **NIH application ID:** 10652174
- **Project number:** 2R15GM132816-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Marino JE Resendiz
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $458,356
- **Award type:** 2
- **Project period:** 2019-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10652174

## Citation

> US National Institutes of Health, RePORTER application 10652174, 8-Oxo-7,8-dihydroguanosine in aptamer development and its impact on RNA structure (2R15GM132816-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10652174. Licensed CC0.

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