# SMALL-MOLECULE AND NUCLEIC ACID ENGINEERING TOWARD MOLECULAR DESIGNS OF THERAPEUTIC POTENTIAL

> **NIH NIH R35** · RUTGERS, THE STATE UNIV OF N.J. · 2024 · $388,621

## Abstract

PROJECT SUMMARY / ABSTRACT
Designer small molecules and nucleic acid polymers are essential to the advancement of biotechnology and
precision medicine. However, efforts to develop such molecules with therapeutic potential face significant
challenges with regard to target selectivity, efficacy, and biostability. These challenges present critical barriers
to progress in clinical applications. Our long-term goal is to address these challenges by combining synthetic
organic chemistry and nucleic acid engineering toward sophisticated molecular designs as modulators of
disease-related targets or pathways. To achieve our goal, we propose the following research programs in this
MIRA application: 1) We will develop novel ligand-heterocycle conjugates as high-performing targeted RNA
degraders. These conjugates will exhibit rapid RNA degradation kinetics along with excellent selectivity for
G-quadruplexes found in RNAs associated with cancer; 2) We will engineer nucleic acid polymers with
(thio)phosphoramidate backbones that can serve as biostable mimics of RNA-cleaving ribozymes. In addition,
we will develop cyclic (thio)phosphoramidate dinucleotides as biostable agonists of the cGAS–STING
pathway, a critical mediator of inflammation; and 3) We will enhance the therapeutic potentials of nucleic acid
catalysts (NAzymes) by introducing programmable RNA cleavage functionality. Trans-acting NAzymes that
cleave RNA targets will be selectively activated by biochemical agents prevalent in disease conditions,
reducing damage to healthy cells. Realization of the proposed design principles will help advance the field of
nucleic acid therapy and drug development efforts geared toward precision medicine. The proposed research
projects will establish a foundation for promoting diversity and inclusivity, with opportunities for cross-
institutional collaborations and professional development.

## Key facts

- **NIH application ID:** 10941353
- **Project number:** 1R35GM155002-01
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Enver C Izgu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,621
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941353

## Citation

> US National Institutes of Health, RePORTER application 10941353, SMALL-MOLECULE AND NUCLEIC ACID ENGINEERING TOWARD MOLECULAR DESIGNS OF THERAPEUTIC POTENTIAL (1R35GM155002-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10941353. Licensed CC0.

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