Bacteriophage lambda: The path from biology to theranostic agent

Abstract

Viral particles provide an attractive platform for the engineering of semisynthetic therapeutic nanoparticles. They can be modified both genetically and chemically in a defined manner to alter their surface characteristics, for targeting specific cell types, to improve their pharmacokinetic features and to attenuate (or enhance) their antigenicity. These advantages derive from a detailed understanding of virus biology, gleaned from decades of fundamental genetic, biochemical, and structural studies that have provided mechanistic insight into virus assembly pathways. In particular, bacteriophages offer significant advantages as nanoparticle platforms and several have been adapted toward the design and engineering of "designer" nanoparticles for therapeutic and diagnostic (theranostic) applications. The present review focuses on one such virus, bacteriophage lambda; I discuss the biology of lambda, the tools developed to faithfully recapitulate the lambda assembly reactions in vitro and the observations that have led to cooptation of the lambda system for nanoparticle design. This discussion illustrates how a fundamental understanding of virus assembly has allowed the rational design and construction of semisynthetic nanoparticles as potential theranostic agents and illustrates the concept of benchtop to bedside translational research. This article is categorized under: Biology-Inspired Nanomaterials> Protein and Virus-Based Structures Biology-Inspired Nanomaterials> Nucleic Acid-Based Structures.

Bacteriophage T4 nanoparticles for vaccine delivery against infectious diseases

“…Unlike the phage T4 Soc, gpD is essential to stabilize the capsid against the internal pressure of the packaged 48.5 kb phage genome inside [158]. However, gpD can be dispensable for capsids carrying shorter genomes [158, 159] and has been extensively used for peptide display [160]. Although both the NH2- and COOH-termini could be used for fusion of antigen peptides [28, 31, 161], the apparent interaction of the NH2-terminus with gpE makes it less desirable [162].…”

Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease

“…The Catalano laboratory has developed a "designer nanoparticle" platform adapted from phage lambda (47). Co-expression of the major capsid and "scaffolding" proteins in Escherichia coli affords icosahedral PLP shells that can be isolated in high yield.…”

The phage L capsid decoration protein has a novel OB-fold and an unusual capsid binding strategy

“…Defining the mechanisms by which different decoration proteins, such as gpD and Dec, bind viral particle surfaces is not only important for understanding the underlying biology, but is also critical for (1) the potential exploitation of phages in nanomedicine (Tao et al, 2018b; Tao et al, 2018a; Vernhes et al, 2017; Asija and Teschke, 2018; Serwer and Wright, 2018), (2) structure-guided design of virus-inspired nanomaterials (Sharma et al, 2017; Parent et al, 2012b; Douglas and Young, 2006; Schwarz et al, 2015; McCoy et al, 2018; Catalano, 2018), and (3) shedding light on capsid assembly and stabilization processes (Teschke and Parent, 2010; Suhanovsky and Teschke, 2015). We report the structure of phage L Dec protein, which has a novel fold for a decoration protein and propose an explanation for how Dec may be able to bind to subtly different capsid binding sites.…”