# Development and Utilization of Splice-specific Antibodies

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT STORRS · 2021 · $169,080

## Abstract

ABSTRACT
In the human genome, alternative splicing events facilitate the generation of a proteome with a
greater diversity than is observed in the protein-coding gene repertoire. In other words, the vast
majority of human genes can each produce numerous different transcripts and subsequently multiple
protein isoforms. However, aberrant splicing can produce an increase in novel isoforms or normally
low-level isoforms leading to potentially detrimental effects including altered protein function, protein-
protein interactions as well as remodeling of protein complexes and pathways. In fact, the increase
in these alternatively-spliced isoforms is now recognized as a major contributor to oncogenic
phenotypes, such as the development of tumors and new blood vessels by supporting cell invasion
and proliferation. A central challenge to realizing the biological impact, prognostic and therapeutic
potential of alternatively-spliced isoforms across multiple cancer types has been a lack of technology
available for unambiguously differentiating highly similar protein variants in their native forms. Current
methods of detecting and studying alternatively-spliced isoforms at the protein level rely solely on
indirect methods such as tag-based detection and nonspecific affinity reagents that are unable to
discriminate among multiple protein isoforms. Herein, we propose a novel approach to develop highly
specific antibodies against alternatively-spliced protein isoforms using a targeting method at the
splice site junction with near amino acid specificity. With this technology, antibodies can be generated
to specifically detect a desired, alternatively-spliced protein isoform without cross-reactivity to the native
full-length form. This technological advance will accelerate oncology research and enable scientists
to study both high-value and novel protein isoforms and their direct role in specific cancer
phenotypes, metastatic potential, tumor grade specificity and survival rates, and provide a validation
means for assessing the therapeutic potential of anticancer alternative-splicing inhibitors.

## Key facts

- **NIH application ID:** 10242818
- **Project number:** 5R21CA240199-03
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Rachel O'Neill
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $169,080
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242818

## Citation

> US National Institutes of Health, RePORTER application 10242818, Development and Utilization of Splice-specific Antibodies (5R21CA240199-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10242818. Licensed CC0.

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