An amino acid substitution in a capsid protein enhances phage survival in mouse circulatory system more than a 1000-fold

Vitiello, Carmen; Merril, Carl R.; Adhya, Sankar

doi:10.1016/j.virusres.2005.05.014

Cited by 83 publications

(55 citation statements)

References 5 publications

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“…The clearance kinetics of viruses have been reported in several instances, including our prior work with CPMV [46] and, most notably, studies of adenovirus (Ad) and bacteriophages [20,53,56]. In general, particulate materials including viruses are removed from the bloodstream relatively quickly by the reticulo-endothelial system (RES) of the liver and spleen [17,42].…”

Section: Discussionmentioning

confidence: 99%

“…When T7 phage is administered intravenously amounts of circulating particles decline to negligible levels within one hour [53]. In contrast, the lambda phage particles survived longer in circulation, and a single amino acid change from lysine to glutamic acid in the coat protein was reported to extend the circulation time by 3 to 4 orders of magnitude [56], suggesting that surface interactions between the phage, immune system and vascular endothelial cells have a significant effect on plasma clearance.…”

Section: Discussionmentioning

confidence: 99%

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Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

Singh

Prasuhn

Yeh

et al. 2007

Journal of Controlled Release

227

224

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Virus-based nanoparticles (VNPs) from a variety of sources are being developed for biomedical and nanotechnology applications that include tissue targeting and drug delivery. However, the fate of most of those particles in vivo has not been investigated. Cowpea mosaic virus (CPMV), a plant comovirus, has been found to be amenable to the attachment of a variety of molecules to its coat protein, as well as to modification of the coat protein sequence by genetic means. We report here the results of studies of the bio-distribution, toxicology, and pathology of CPMV in mice. Plasma clearance and tissue biodistribution were measured using CPMV particles derivatized with lanthanide metal complexes. CPMV particles were cleared rapidly from plasma, falling to undetectable levels within 20 minutes. By 30 minutes the majority of the injected VNPs were trapped in the liver and to a lesser extent the spleen with undetectable amounts in other tissues. At doses of 1 mg, 10 mg and 100 mg per kg body weight, no toxicity was noted and the mice appeared to be normal. Hematology was essentially normal, although with the highest dose examined, the mice were somewhat leukopenic with relative decreases in both neutrophils and lymphocytes. Histological examination of spleen showed cellular infiltration, which upon flow cytometry analyses revealed elevated B lymphocytes on the first day following virus administration that subsequently subsided. Microscopic evaluation of various other tissues revealed a lack of apparent tissue degeneration or necrosis. Overall, CPMV appears to be a safe and non-toxic platform for in vivo biomedical applications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

Singh

Prasuhn

Yeh

et al. 2007

Journal of Controlled Release

227

224

View full text Add to dashboard Cite

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“…Molenaar et al (2002), for example, showed that simply displaying peptides on phage could modify their natural pharmacokinetics when injected into mice. Indeed, the possibility of creating phage with altered pharmacokinetics when administered in vivo was first reported several years ago (Geier et al 1973; Merril et al 1996) and attributed to single-amino-acid changes in coat composition (Vitiello et al 2005). Although their safety in humans (Bruttin and Brussow 2005) suggests that T4 phage may be an optimal starting point for directed evolution of a vector, we have focused on filamentous M13 phage (Larocca et al 2002b), whereas other investigators have turned to similar approaches using mammalian viral systems (Spear et al 2003; Perabo et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Gene Transfer into Mammalian Cells Using Targeted Filamentous Bacteriophage

Baird¹

2011

Cold Spring Harb Protoc

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INTRODUCTIONPhage vectors, because of their genetic simplicity, are uniquely suited to methods that use directed evolution to genetically optimize vectors for therapeutic gene delivery. Moreover, because phage production is restricted to strain-specific bacteria, the hosts are equally amenable to genetic engineering, modification, and even genetic selections to optimize yield, genetic stability, manufacture, and cost. The choice of targeting ligand determines the specificity of targeted phage transduction. Genetic targeting is limited to proteins that can be efficiently expressed and biologically active following secretion into the periplasmic space of the bacteria and subsequent incorporation into the phage particle. The capacity of phage to display a chosen targeting ligand must be determined empirically and optimized. Alternatively, the targeting ligand can be selected after display in a phage library. The orientation of the reporter gene relative to the phage structural genes can affect vector transduction efficiency. We have also targeted phage particles for gene delivery using an avidin-biotin linkage. This allows selection of ligands without concern for their ability to be displayed genetically. This protocol describes the use of targeted filamentous phage for gene delivery to mammalian cells. The final vector, although of low efficiency, is meant to serve as a starting point for a vector development platform that can use in vitro and in vivo techniques of combinatorial display to direct its evolution to high efficiency, high specificity, and eventually, safety in humans.

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“…Animal studies have clearly shown that most phage are taken up by the liver with some trapping by the spleen (Merril et al 2003). In some cases, it has been possible to select phage strains that can remain in the circulation, and remain available for interaction with possible systemic bacterial infectious agents by genetic selection methods (Merril et al 1996;Vitiello et al 2005). In a similar manner it should be possible to select phage strains that have a reduced immunogenicity.…”

Section: Potential Problems For Use Of Phage As Antibacterial Therapymentioning

confidence: 99%

Therapeutic and Prophylactic Applications of Bacteriophage Components in Modern Medicine

Adhya

Merril

Biswas

2014

Cold Spring Harbor Perspectives in Medicine

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Correspondence: sadhya@helix.nih.govAs the interactions of phage with mammalian innate and adaptive immune systems are better delineated and with our ability to recognize and eliminate toxins and other potentially harmful phage gene products, the potential of phage therapies is now being realized. Early efforts to use phage therapeutically were hampered by inadequate phage purification and limited knowledge of phage-bacterial and phage-human relations. However, although use of phage as an antibacterial therapy in countries that require controlled clinical studies has been hampered by the high costs of patient trials, their use as vaccines and the use of phage components such as lysolytic enzymes or lysozymes has progressed to the point of commercial applications. Recent studies concerning the intimate associations between mammalian hosts and bacterial and phage microbiomes should hasten this progress.

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An amino acid substitution in a capsid protein enhances phage survival in mouse circulatory system more than a 1000-fold

Cited by 83 publications

References 5 publications

Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo

Gene Transfer into Mammalian Cells Using Targeted Filamentous Bacteriophage

Therapeutic and Prophylactic Applications of Bacteriophage Components in Modern Medicine

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