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Liquid-Liquid Phase Separation Enables Highly Selective Viral Genome Packaging

Layne B. Frechette and Michael F. Hagan*

  • *Contact author: hagan@brandeis.edu
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PRX Life 4, 013013 – Published 2 February, 2026

DOI: https://doi.org/10.1103/kx13-czqb

Abstract

In many viruses, hundreds of proteins assemble an outer shell (capsid) around the viral nucleic acid to form an infectious virion. How the assembly process selects the viral genome amidst a vast excess of diverse cellular nucleic acids is poorly understood. It has recently been discovered that many viruses perform assembly and genome packaging within liquid-liquid phase separated biomolecular condensates inside the host cell. However, the role of condensates in genome packaging is poorly understood. Here, we construct equilibrium and dynamical rate equation models for condensate-coupled assembly and genome packaging. We show that when the viral genome and capsid proteins favorably partition into the condensate, assembly rates, yields, and packaging efficiencies can increase by orders of magnitude. Selectivity is further enhanced by the condensate when capsid proteins are translated during assembly and packaging. Our results suggest that viral condensates provide a mechanism to ensure robust and highly selective assembly of virions around viral genomes. More broadly, our results may apply to other types of selective co-assembly processes that occur within biomolecular condensates and suggest that liquid-liquid phase-separated condensates could be exploited for selective encapsulation of microscopic cargo in human-engineered systems.

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Collection on Physics of Biomolecular Condensates

From the fundamentals of phase separation, dynamics and structure of condensates in biological settings, to advanced imaging methods, this special collection presented by PRX Life showcases exciting and timely work on the physics of biomolecular condensates.

This Invited Collection is coordinated by PRX Life Associate Editor Christoph Weber, in consultation with Jerelle Joseph, Simon Alberti, and Tanja Mittag. Every article published in this collection underwent a rigorous peer review process, adhering to the same high standards applied to all papers handled by the journal. The PRX Life editorial team managed the peer review and made all editorial decisions.

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PRX Life 4, 013013– Published 2 February, 2026
  • Received 26 August 2025
  • Accepted 19 December 2025
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