Novel tracing paradigms—genetically engineered herpesviruses as tools for mapping functional circuits within the CNS: present status and future prospects

Boldogköi, Zsolt; Sı́k, Attila; Dénes, Ádám; Reichart, Anikó; Toldi, József; Gerendai, Ida; Kovács, Krisztina; Palkovits, Miklós

doi:10.1016/j.pneurobio.2004.03.010

Cited by 75 publications

(59 citation statements)

References 147 publications

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“…Understanding how nucleic acid-protein interactions drive cooperative assembly could enable antiviral drugs that block this essential step in viral replication. At the same time, engineered structures in which viral capsids assemble around synthetic cargoes show a great promise as delivery vehicles for drugs [1][2][3] or imaging agents [4][5][6][7] and as subunits or templates for the synthesis of advanced multicomponent nanomaterials. [8][9][10][11][12] Realizing these goals, however, requires understanding at a fundamental level of how properties of cargoes and capsid proteins control assembly rates and mechanisms.…”

Section: Introductionmentioning

confidence: 99%

A theory for viral capsid assembly around electrostatic cores

Hagan¹

2009

The Journal of Chemical Physics

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We develop equilibrium and kinetic theories that describe the assembly of viral capsid proteins on a charged central core, as seen in recent experiments in which brome mosaic virus capsids assemble around nanoparticles functionalized with polyelectrolyte. We model interactions between capsid proteins and nanoparticle surfaces as the interaction of polyelectrolyte brushes with opposite charge using the nonlinear Poisson Boltzmann equation. The models predict that there is a threshold density of functionalized charge, above which capsids efficiently assemble around nanoparticles, and that light scatter intensity increases rapidly at early times without the lag phase characteristic of empty capsid assembly. These predictions are consistent with and enable interpretation of preliminary experimental data. However, the models predict a stronger dependence of nanoparticle incorporation efficiency on functionalized charge density than measured in experiments and do not completely capture a logarithmic growth phase seen in experimental light scatter. These discrepancies may suggest the presence of metastable disordered states in the experimental system. In addition to discussing future experiments for nanoparticle-capsid systems, we discuss broader implications for understanding assembly around charged cores such as nucleic acids.

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Section: Introductionmentioning

confidence: 99%

A theory for viral capsid assembly around electrostatic cores

Hagan¹

2009

The Journal of Chemical Physics

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“…By combining the unparalleled self-assembly and targeting capabilities of viruses with the functionalizability of nanoparticles, VLPs show promise as imaging agents [36][37][38][39], diagnostic and therapeutic vectors [40][41][42], and as subunits or templates for synthesis of advanced nanomaterials [43][44][45][46]. Our models offer a framework with which to interpret experimental results in order to design more efficient templated assembly of nanomaterials, and a means to use this as a model system with which to understand aspects of viral protein assembly around nucleic acid cores.…”

Section: Introductionmentioning

confidence: 99%

Controlling viral capsid assembly with templating

Hagan

2008

Phys. Rev. E

104

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We develop coarse-grained models that describe the dynamic encapsidation of functionalized nanoparticles by viral capsid proteins. We find that some forms of cooperative interactions between protein subunits and nanoparticles can dramatically enhance rates and robustness of assembly, as compared to the spontaneous assembly of subunits into empty capsids. For large core-subunit interactions, subunits adsorb onto core surfaces en masse in a disordered manner, and then undergo a cooperative rearrangement into an ordered capsid structure. These assembly pathways are unlike any identified for empty capsid formation. Our models can be directly applied to recent experiments in which viral capsid proteins assemble around the functionalized inorganic nanoparticles [Sun et al., Proc. Natl. Acad. Sci (2007) 104, 1354. In addition, we discuss broader implications for understanding the dynamic encapsidation of single-stranded genomic molecules during viral replication and for developing multicomponent nanostructured materials.

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“…increasing promise as therapeutic and diagnostic vectors (1)(2)(3)(4)(5)(6), imaging agents (7)(8)(9)(10), and as templates and microreactors for advanced nanomaterials synthesis (11)(12)(13)(14)(15)(16)(17). Here, we address the rules for the formation of symmetric protein cages consisting of viral capsid subunits formed over a functionalized inorganic nanoparticle core, called virus-like particles (VLPs).…”

mentioning

confidence: 99%

Core-controlled polymorphism in virus-like particles

Sun

Dufort²,

Daniel³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

271

363

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This study concerns the self-assembly of virus-like particles (VLPs) composed of an icosahedral virus protein coat encapsulating a functionalized spherical nanoparticle core. The recent development of efficient methods for VLP self-assembly has opened the way to structural studies. Using electron microscopy with image reconstruction, the structures of several VLPs obtained from brome mosaic virus capsid proteins and gold nanoparticles were elucidated. Varying the gold core diameter provides control over the capsid structure. The number of subunits required for a complete capsid increases with the core diameter. The packaging efficiency is a function of the number of capsid protein subunits per gold nanoparticle. VLPs of varying diameters were found to resemble to three classes of viral particles found in cells (T ‫؍‬ 1, 2, and 3). As a consequence of their regularity, VLPs form three-dimensional crystals under the same conditions as the wild-type virus. The crystals represent a form of metallodielectric material that exhibits optical properties influenced by multipolar plasmonic coupling. metamaterials ͉ protein cage ͉ self-assembly ͉ surface plasmon ͉ virus assembly E ngineered virus capsids and protein cage structures have shown increasing promise as therapeutic and diagnostic vectors (1-6), imaging agents (7-10), and as templates and microreactors for advanced nanomaterials synthesis (11)(12)(13)(14)(15)(16)(17). Here, we address the rules for the formation of symmetric protein cages consisting of viral capsid subunits formed over a functionalized inorganic nanoparticle core, called virus-like particles (VLPs).VLPs provide an example of how biomimetic self-organization can combine the natural characteristics of virus capsids with the exquisite physical properties of nanoparticles (18)(19)(20). Interactions between the artificial cargo and the protein carrier affects both the self-assembly and the stability of the resulting structure, yet very little is known about them. Progress toward the basic development and the practical use of VLPs requires an understanding of how relevant parameters contribute to complex formation.Symmetric VLPs may provide a technology for therapeutic or diagnostic agent delivery that is improved over amorphous shell nanoparticles that are already known to be efficient in similar applications (21). The advantage of a regular surface protein motif is that the binding domains are functionally identical by virtue of their equivalent environment. It has been shown in several situations that receptor-mediated targeting can be achieved even when using amorphous coatings (22). However, the principle challenges for nanoparticle delivery currently include: limited life-time in body fluids, nanoparticle transduction across the cellular membrane, avoidance of the exocytotic pathways, and target specificity. To optimize their infectivity, viruses have evolved to overcome these challenges. We still must learn how to apply virus strategies to targeted delivery. A simple question is central to this o...

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Novel tracing paradigms—genetically engineered herpesviruses as tools for mapping functional circuits within the CNS: present status and future prospects

Cited by 75 publications

References 147 publications

A theory for viral capsid assembly around electrostatic cores

A theory for viral capsid assembly around electrostatic cores

Controlling viral capsid assembly with templating

Core-controlled polymorphism in virus-like particles

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