# A Novel Technology for Engineering Binders to Membrane Proteins

> **NIH NIH R21** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2021 · $189,375

## Abstract

Antibodies have been coined the ‘magic bullets’ against many human diseases. However, there remains
significant challenges in the engineering of antibodies targeting multi-pass membrane proteins, which
encompass a large number of therapeutic targets such as cell surface receptors and the ion channel proteins.
The difficulty in engineering binders to membrane proteins stems from the limitation of the current in vitro
selection/panning technologies, such as phage display, which require highly purified target protein.
Unfortunately, membrane proteins are often refractory to purification due to their dependence on the cell
membrane for proper folding and activity. Currently, there is no effective in vitro technology for the
discovery/engineering of binders to multi-pass membrane proteins. The overall goal of this study is to develop
a novel technology – SMURF (Simple proxiMity coUpled mRNA display) – for engineering protein binders to
protein targets on the cell surface, thus bypassing the need to purify the target protein. SMURF combines
mRNA display with the proximity-assisted-DNA-assembly phenomenon and, unlike conventional panning in
which all binders to a solid support are enriched, SMURF fosters the enrichment of binders only to a desired
target protein on the cell surface. In Aim 1, we will demonstrate the SMURF principle using oligonucleotides
and optimize the primer sequences. Aim 2 will establish the SMURF enrichment of a model protein in a
mixture of non-target proteins in solution. Finally, in Aim 3, a model protein will be displayed on the
mammalian cell surface and a library of binders will be screened to demonstrate and quantify the whole-cell
SMURF enrichment efficiency. The successful completion of this study will establish a novel technology for
facile discovery/engineering of binders to whole-cell-displayed membrane proteins and should greatly expand
the repertoire of drug targets amenable to therapeutic intervention.

## Key facts

- **NIH application ID:** 10227122
- **Project number:** 5R21GM138811-02
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Zhilei Chen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $189,375
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227122

## Citation

> US National Institutes of Health, RePORTER application 10227122, A Novel Technology for Engineering Binders to Membrane Proteins (5R21GM138811-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10227122. Licensed CC0.

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