Nanomedicine and Phage Capsids

Abstract

Studies of phage capsids have at least three potential interfaces with nanomedicine. First, investigation of phage capsid states potentially will provide therapies targeted to similar states of pathogenic viruses. Recently detected, altered radius-states of phage T3 capsids include those probably related to intermediate states of DNA injection and DNA packaging (dynamic states). We discuss and test the idea that some T3 dynamic states include extensive α-sheet in subunits of the capsid’s shell. Second, dynamic states of pathogenic viral capsids are possible targets of innate immune systems. Specifically, α-sheet-rich innate immune proteins would interfere with dynamic viral states via inter-α-sheet co-assembly. A possible cause of neurodegenerative diseases is excessive activity of these innate immune proteins. Third, some phage capsids appear to have characteristics useful for improved drug delivery vehicles (DDVs). These characteristics include stability, uniformity and a gate-like sub-structure. Gating by DDVs is needed for (1) drug-loading only with gate opened; (2) closed gate-DDV migration through circulatory systems (no drug leakage-generated toxicity); and (3) drug release only at targets. A gate-like sub-structure is the connector ring of double-stranded DNA phage capsids. Targeting to tumors of phage capsid-DDVs can possibly be achieved via the enhanced permeability and retention effect.

A Protein Assembly Hypothesis for Population-Specific Decrease in Dementia with Time

“…More recently, yet additional data suggest that the details of this innate immune reaction are the following [11,12]. 1The structural basis is a (self-complementary) sheetlike protein structure, originally discovered by Pauling and Corey [13], and later called α-sheet [14][15][16].…”

“…This rotation places all α-carboxyl groups (negatively charged at neutral pH) on one edge of the sheet and all α-amino groups (positively charged at neutral pH) on the opposite edge. Based on observation and characterization of DNA packaging-generated hyper-expanded capsids (details, below), α-sheet is proposed to be a major conformation of virus capsid proteins during virus assembly [11,12]. However, in healthy human cells, α-sheet is present only in stretches of 4-6 amino acids [14,15].…”

“…Some DNA packaginggenerated capsids are hyper-expanded, as illustrated in Figure 1b. The hyper-expansion constrains these capsids to have an outer shell so thin that the protein subunits of the capsid's outer shell must have a sheet structure [11,12]. This structure is likely to be α-sheet for the following reasons.…”

Bacteriophage-Based Biotechnological Applications

“…Besides targeting infectious diseases, phages have been proposed as drug delivery vehicles to treat neurogenerative diseases. Philip Serwer and Elena T. Wright [6] have given their opinion on the application of phages in nanomedicine, discussing how phages (more specifically their capsids) can be applied to treat diseases such as Alzheimer’s, Parkinson’s, or even cancer.…”

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.…”