Nanobody-Based BioPROTAC for Cellular Degradation of PRL3 in Cancer Cells

Faculty Mentor

Mark V. C. dela Cerna

Location

Savannah Ballroom

Type of Research

On-going

Session Format

Poster Presentation

College

College of Science & Mathematics

Department

Department of Biochemistry, Chemistry, and Physics

Abstract

Phosphatase of Regenerating Liver 3 (PRL3), a member of the PTP family, is associated with tumor growth and metastasis via its role in activating harmful oncogenic cell pathways, has solidified as a good target for cancer therapy. However, to date, there is still no approved therapeutic modality targeting PRL3, therefore there is a critical need for development of such. One approach that is being employed in targeting PRL3 is the development of nanobodies, which are small proteins derived from the variable region of heavy chain only antibodies of camelids. Nanobodies can be used as therapeutics and in diagnostics as they can be engineered for high target affinity and their size means they can penetrate tissues more effectively. Additionally, they can be produced using E. coli, and are therefore cheaper and easier to produce than monoclonal antibodies. From a NB library that was developed to specifically target PRL3, NB91 was selected to develop a nanobody based degrader because of its high affinity for PRL3. The degrader utilizes a miniprotein to deliver a nanobody attached to an E3 adaptor to recruit ubiquitin ligase, allowing the Nb to direct its recognized target for degradation. This cell permeable degrader is specifically designed to be used against PRL3 as an alternative to small molecule inhibitors, in hopes to be developed for clinical applications against PRL3 for various cancers and metastasis. Efforts to optimize expression and purification of this NB91 based degrader are underway and will be followed with testing its cellular uptake and efficacy in PRL3 degradation.

Program Description

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Start Date

4-21-2026 10:00 AM

End Date

4-21-2026 12:00 PM

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Apr 21st, 10:00 AM Apr 21st, 12:00 PM

Nanobody-Based BioPROTAC for Cellular Degradation of PRL3 in Cancer Cells

Savannah Ballroom

Phosphatase of Regenerating Liver 3 (PRL3), a member of the PTP family, is associated with tumor growth and metastasis via its role in activating harmful oncogenic cell pathways, has solidified as a good target for cancer therapy. However, to date, there is still no approved therapeutic modality targeting PRL3, therefore there is a critical need for development of such. One approach that is being employed in targeting PRL3 is the development of nanobodies, which are small proteins derived from the variable region of heavy chain only antibodies of camelids. Nanobodies can be used as therapeutics and in diagnostics as they can be engineered for high target affinity and their size means they can penetrate tissues more effectively. Additionally, they can be produced using E. coli, and are therefore cheaper and easier to produce than monoclonal antibodies. From a NB library that was developed to specifically target PRL3, NB91 was selected to develop a nanobody based degrader because of its high affinity for PRL3. The degrader utilizes a miniprotein to deliver a nanobody attached to an E3 adaptor to recruit ubiquitin ligase, allowing the Nb to direct its recognized target for degradation. This cell permeable degrader is specifically designed to be used against PRL3 as an alternative to small molecule inhibitors, in hopes to be developed for clinical applications against PRL3 for various cancers and metastasis. Efforts to optimize expression and purification of this NB91 based degrader are underway and will be followed with testing its cellular uptake and efficacy in PRL3 degradation.