ORIGINAL RESEARCH article
Front. Drug Discov.
Sec. Technologies and Strategies to Enable Drug Discovery
Multivalent display of membrane proteins using HIV1-Gag VLPs
Provisionally accepted
Neha A. Bhat1
Nicholas Dunn2Xiaodi Yu1Matthew DuPrie1Supratik Dutta1
Matt McLean1Micheal D. Feldkamp1Jacqueline Kratch1Mandeep K. Mann1Simin Rahighi1Robert C. Davidson1
John Leppard1Gabriel Cheung1
Puneet Khandelwal3*- 1Johnson and Johnson, Spring House, United States
- 2Frontage Laboratories Inc, Exton, United States
- 3Johnson & Johnson, Washington, D.C., United States
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Membrane proteins are increasingly becoming attractive targets for biotherapeutics, but their production is challenging due to extraction with detergents that often results in low yields and purity, and potential changes in conformation. In this study, we evaluated HIV-1 Gag Virus Like Particles (VLPs) for the display of heterologous membrane proteins in their native conformation and lipid environment. We have developed a scalable workflow for purification of VLPs from HEK293T that are pseudotyped with recombinant membrane proteins. This method results in pure, stable and monodisperse particles that display membrane proteins in their native conformation and are suitable for downstream applications. Furthermore, we have developed method for site-specific conjugation of biotin on the VLP surface using a dual snorkel-sortase tag which does not affect, size, purity, or antigen expression and conformation. We used biotinylated membrane protein pseudotyped VLPs in the SPR assay to determine binding kinetics for an internal biotherapeutic. Altogether, these advances open avenues for incorporation of VLPs to advance antibody discovery for critical membrane targets.
Keywords: biologics, VLP, Gag, membrane protein, Snorkel, sortase
Received: 18 Aug 2025; Accepted: 09 Dec 2025.
Copyright: © 2025 Bhat, Dunn, Yu, DuPrie, Dutta, McLean, Feldkamp, Kratch, Mann, Rahighi, Davidson, Leppard, Cheung and Khandelwal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Puneet Khandelwal
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