# Chimeric Ligands for Induced Proximity (CLIP) platform for targeted proteome editing and upregulation of antigen presentation

> **NIH NIH R41** · UBIQUITX, INC. · 2024 · $299,921

## Abstract

Abstract
UbiquiTx is developing a programmable, modular therapeutic platform for the direct modification of proteins of
interest (POIs). Leveraging advances in artificial intelligence, protein engineering, and mRNA as a therapeutic
modality, this platform allows for the engineering of enzymes to precisely recognize and ‘edit’ POIs by
installing/removing post-translational modifications (PTMs). As one therapeutic application for this technology,
UbiquiTx seeks to enhance the immune targeting of diseased cells through the upregulation of selective antigen
presentation on the cell surface. T cells play a central role in immunosurveillance against viruses, other
intracellular pathogens, and cancers by recognizing short peptides presented by major histocompatibility
complex (MHC) class I molecules. These antigenic peptides are generated from proteins processed through the
ubiquitin-proteasome system, then loaded onto MHC I molecules and transported to the cell surface for
immunosurveillance. Global downregulation of antigen presentation on the cell surface is a major mechanism by
which cells escape this immune surveillance, allowing diseased cells to proliferate. Thus, overcoming MHC-I
downregulation and restoring antigen presentation represents a promising avenue for enhancing the efficacy of
and patient response to immune-based therapies.
UbiquiTx’s Chimeric Ligands for Induced Proximity (CLIPs) comprise a computationally designed guide peptide
targeting a specific POI that is fused with a protein modification enzyme component. Preliminary data has
provided compelling proof-of-concept, demonstrating the platform ability to design high-affinity peptide binders
to POIs, that swap out modification enzymes and deliver CLIPs as an mRNA therapeutic using a lipid
nanoparticle (LNP) vehicle. In this Phase I project, UbiquiTx will utilize the platform to upregulate the presentation
of disease-associated peptide antigens by MHC-I, enhancing the immune surveillance of diseased cells. CLIPs
will be designed and evaluated to promote the degradation of three key POIs: WT1, PRAME, and E7. WT1 is an
intracellular, oncogenic transcription factor present in a wide range of leukemias and solid cancers, while PRAME
is a cancer-testis antigen that provides a target for immunotherapy in acute myeloid leukemia. E7 is a human
papillomavirus (HPV)-derived protein and target for the treatment of HPV-driven cancers. Evaluating these
targets will demonstrate UbiquiTx’s platform modularity, ability to target proteins with variable expression, as well
as degrade endogenous host- and virus-derived oncogenic proteins. The proposed Specific Aims are: 1. Develop
and characterize ubiquitinase CLIPs (ubiCLIPs) for WT1, PRAME, and E7 and perform in vitro characterization
to assess target engagement and protein degradation. 2. Evaluate WT1 antigen presentation and recognition by
TCRm. UbiquiTx’s collaborator, Dr. David Scheinberg, will assess the effect of the top performing WT1 ubiCLIP...

## Key facts

- **NIH application ID:** 11006699
- **Project number:** 1R41AI186686-01
- **Recipient organization:** UBIQUITX, INC.
- **Principal Investigator:** Peter Fekkes
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $299,921
- **Award type:** 1
- **Project period:** 2024-07-10 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11006699

## Citation

> US National Institutes of Health, RePORTER application 11006699, Chimeric Ligands for Induced Proximity (CLIP) platform for targeted proteome editing and upregulation of antigen presentation (1R41AI186686-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11006699. Licensed CC0.

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