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1.
As biological agents, viruses come in an astounding range of sizes, with varied shapes and surface morphologies. The structures of viral capsids are generally assemblies of hundreds of copies of one or a few proteins which can be harnessed for use in a wide variety of applications in biotechnology, nanotechnology, and medicine. Despite their complexity, many capsid types form as homogenous populations of precise geometrical assemblies. This is important in both medicine, where well-defined therapeutics are critical for drug performance and federal approval, and nanotechnology, where precise placement affects the properties of the desired material. Here we review the production of viruses and virus-like particles with methods for selecting and manipulating the size, surface chemistry, assembly state, and interior cargo of capsid. We then discuss many of the applications used in research today and the potential commercial and therapeutic products from engineered viral capsids. 相似文献
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Ambient particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is the exacerbation of inflammation, especially in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is the generation of oxidative stress by its chemical compounds and metals. Cellular responses to PM-induced oxidative stress include activation of antioxidant defense, inflammation, and toxicity. The proinflammatory effect of PM in the lung is characterized by increased cytokine/chemokine production and adhesion molecule expression. Moreover, there is evidence that ambient PM can act as an adjuvant for allergic sensitization, which raises the possibility that long-term PM exposure may lead to increased prevalence of asthma. In addition to ambient PM, rapid expansion of nanotechnology has introduced the potential that engineered nanoparticles (NP) may also become airborne and may contribute to pulmonary diseases by novel mechanisms that could include oxidant injury. Currently, little is known about the potential adverse health effects of these particles. In this communication, the mechanisms by which particulate pollutants, including ambient PM and engineered NP, exert their adverse effects through the generation of oxidative stress and the impacts of oxidant injury in the respiratory tract will be reviewed. The importance of cellular antioxidant and detoxification pathways in protecting against particle-induced lung damage will also be discussed. 相似文献
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Hawthorne J Musante C Sinha SK White JC 《International journal of phytoremediation》2012,14(4):429-442
The effect of bulk and engineered nanoparticle (NP) Ag, Au, Cu, Si, and C at 250 and 750 mg/L on zucchini biomass, transpiration, and element content was determined. The pH of bulk and NP solutions prior to plant growth frequently differed. Nanoparticle Cu solution pH was significantly higher than bulk Cu, whereas for Ag and C, the NPs had significantly lower pH. Plants were unaffected by Au, regardless of particle size or concentration. NP Ag reduced plant biomass and transpiration by 49-91% compared to equivalent bulk Ag. NP Si at 750 mg/L reduced plant growth and transpiration by 30-51% relative to bulk Si. Bulk and NP Cu were phytotoxic but much of the effect was alleviated by humic acid. The shoot Ag and Cu content did not differ based on particle size or concentration. The accumulation of bulk Au was greater than the NP, but humic acid increased the accumulation of NP and bulk Au by 5.6-fold and 80%, respectively. The uptake of NP Si was 5.6-6.5-fold greater than observed with the bulk element. These findings show that the NPs may have unique phytotoxicity or accumulation patterns and that solution properties can significantly impact particle fate and effects. 相似文献
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Branduardi P Smeraldi C Porro D 《Journal of molecular microbiology and biotechnology》2008,15(1):31-40
Industrial biotechnology and metabolic engineering can offer an innovative approach to solving energy and pollution problems. The potential industrial applications of yeast are reviewed here. 相似文献
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Ryu MH Moskvin OV Siltberg-Liberles J Gomelsky M 《The Journal of biological chemistry》2010,285(53):41501-41508
Cyclic nucleotides, cAMP and cGMP, are ubiquitous second messengers that regulate metabolic and behavioral responses in diverse organisms. We describe purification, engineering, and characterization of photoactivated nucleotidyl cyclases that can be used to manipulate cAMP and cGMP levels in vivo. We identified the blaC gene encoding a putative photoactivated adenylyl cyclase in the Beggiatoa sp. PS genome. BlaC contains a BLUF domain involved in blue-light sensing using FAD and a nucleotidyl cyclase domain. The blaC gene was overexpressed in Escherichia coli, and its product was purified. Irradiation of BlaC in vitro resulted in a small red shift in flavin absorbance, typical of BLUF photoreceptors. BlaC had adenylyl cyclase activity that was negligible in the dark and up-regulated by light by 2 orders of magnitude. To convert BlaC into a guanylyl cyclase, we constructed a model of the nucleotidyl cyclase domain and mutagenized several residues predicted to be involved in substrate binding. One triple mutant, designated BlgC, was found to have photoactivated guanylyl cyclase in vitro. Irradiation with blue light of the E. coli cya mutant expressing BlaC or BlgC resulted in the significant increases in cAMP or cGMP synthesis, respectively. BlaC, but not BlgC, restored cAMP-dependent growth of the mutant in the presence of light. Small protein sizes, negligible activities in the dark, high light-to-dark activation ratios, functionality at broad temperature range and physiological pH, as well as utilization of the naturally occurring flavins as chromophores make BlaC and BlgC attractive for optogenetic applications in various animal and microbial models. 相似文献
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Klug A 《FEBS letters》2005,579(4):892-894
It has long been the goal of molecular biologists to design DNA-binding proteins for the specific control of gene expression. The zinc finger design is ideally suited for such purposes, discriminating between closely related sequences both in vitro and in vivo. Whereas other DNA-binding proteins generally make use of the 2-fold symmetry of the double helix, zinc fingers do not and so can be linked linearly in tandem to recognize DNA sequences of different lengths, with high fidelity. This modular design offers a large number of combinatorial possibilities for the specific recognition of DNA. By fusing zinc finger peptides to repression or activation domains, genes can be selectively targeted and switched off and on. Several recent applications of such engineered zinc finger proteins (ZFPs) are described, including the activation of vascular endothelial growth factor (VEGF) in a human cell line and an animal model. Clinical trials have recently begun on using VEGF-activating ZFPs to treat human peripheral arterial disease, by stimulating vascular growth. Also in progress are pre-clinical studies using ZFPs to target the defective genes in two monogenic disorders, SCID and SCA. The aim is to replace them in each case by a correct copy from an extrachromosomal DNA donor by means of homologous recombination. Promising results are reported. 相似文献
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Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging 总被引:14,自引:0,他引:14
Lee JH Huh YM Jun YW Seo JW Jang JT Song HT Kim S Cho EJ Yoon HG Suh JS Cheon J 《Nature medicine》2007,13(1):95-99
Successful development of ultra-sensitive molecular imaging nanoprobes for the detection of targeted biological objects is a challenging task. Although magnetic nanoprobes have the potential to perform such a role, the results from probes that are currently available have been far from optimal. Here we used artificial engineering approaches to develop innovative magnetic nanoprobes, through a process that involved the systematic evaluation of the magnetic spin, size and type of spinel metal ferrites. These magnetism-engineered iron oxide (MEIO) nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance imaging (MRI) sensitivity for the detection of cancer markers compared with probes currently available. Also, we successfully visualized small tumors implanted in a mouse. Such high-performance, nanotechnology-based molecular probes could enhance the ability to visualize other biological events critical to diagnostics and therapeutics. 相似文献
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Arvizo RR Miranda OR Moyano DF Walden CA Giri K Bhattacharya R Robertson JD Rotello VM Reid JM Mukherjee P 《PloS one》2011,6(9):e24374
BACKGROUND: Inorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little is known how the surface chemistry of nanoparticles influences their pharmacokinetics, tumor uptake, and biodistribution. METHOD/PRINCIPAL FINDINGS: Using a family of structurally homologous nanoparticles we have investigated how pharmacological properties including tumor uptake and biodistribution are influenced by surface charge using neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH) and positive (TTMA) nanoparticles. Nanoparticles were injected into mice (normal and athymic) either in the tail vein or into the peritoneum. CONCLUSION: Neutral and zwitterionic nanoparticles demonstrated longer circulation time via both i.p. and i.v. administration, whereas negatively and positively charged nanoparticles possessed relatively short half-lives. These pharmacological characteristics were reflected on the tumor uptake and biodistribution of the respective nanoparticles, with enhanced tumor uptake by neutral and zwitterionic nanoparticles via passive targeting. 相似文献
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Field applications of genetically engineered microorganisms for bioremediation processes 总被引:9,自引:0,他引:9
Genetically engineered microorganisms (GEMs) have shown potential for bioremediation applications in soil, groundwater, and activated sludge environments, exhibiting enhanced degradative capabilities encompassing a wide range of chemical contaminants. However, the vast majority of studies pertaining to genetically engineered microbial bioremediation are supported by laboratory-based experimental data. In general, relatively few examples of GEM applications in environmental ecosystems exist. Unfortunately, the only manner in which to fully address the competence of GEMs in bioremediation efforts is through long-term field release studies. It is therefore essential that field studies be performed to acquire the requisite information for determining the overall effectiveness and risks associated with GEM introduction into natural ecosystems. 相似文献
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Nanotechnology is relevant to diverse fields of science and technology. Due to the many advantages over non-biological systems,
several research groups have exploited the use of biological systems for the synthesis of nanoparticles. Among the different
microbes used for the synthesis of nanoparticles, fungi are efficient candidates for fabrication of metal nanoparticles both
intra- and extracellulary. The nanoparticles synthesized using fungi present good polydispersity, dimensions and stability.
The potential applications of nanotechnology and nanoparticles in different fields have revolutionized the health care, textile
and agricultural industries and they are reviewed here. 相似文献
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We have developed a portable biosensing device based on genetically engineered bioluminescent (BL) cells. Cells were immobilized on a 4 × 3 multiwell cartridge using a new biocompatible matrix that preserved their vitality. Using a fiber optic taper, the cartridge was placed in direct contact with a cooled CCD sensor to image and quantify the BL signals. Yeast and bacterial cells were engineered to express recognition elements, whose interaction with the analyte led to luciferase expression, via reporter gene technology. Three different biosensors were developed. The first detects androgenic compounds using yeast cells carrying a green-emitting P. pyralis luciferase regulated by the human androgen receptor and a red mutant of the same species as internal vitality control. The second biosensor detects two classes of compounds (androgens and estrogens) using yeast strains engineered to express green-or red-emitting mutant firefly luciferases in response to androgens or estrogens, respectively. The third biosensor detects lactose analogue isopropyl β-d-1-thiogalactopyranoside using two E. coli strains. One strain exploits the lac operon as recognition element for the expression of P. pyralis luciferase. The other strain serves as a vitality control expressing Gaussia princeps luciferase, which requires a different luciferin substrate. The immobilized cells were stable for up to 1 month. The analytes could be detected at nanomolar levels with good precision and accuracy when the specific signal was corrected using the internal vitality control. This portable device can be used for on-site multiplexed bioassays for different compound classes. 相似文献
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An engineered superantigen SEC2 exhibits promising antitumor activity and low toxicity 总被引:1,自引:0,他引:1
Xu M Wang X Cai Y Zhang H Yang H Liu C Zhang C 《Cancer immunology, immunotherapy : CII》2011,60(5):705-713
Recent studies suggested that the histidine residues at 118 and 122 play an important role for the toxicity of staphylococcal
enterotoxin C subtype 2 (SEC2), and the substitutions of both histidines with alanine can severely impair the fever activity
of SEC2. We hypothesized that promising SEC2 antitumor agent with low toxicity and enhanced superantigen activity can be constructed
by introducing related mutations at protein functional sites of SEC2. We showed that the SEC2 mutants H122A and H118A/H122A
exhibited improved superantigen activity after introducing the point mutations at Thr20 and Gly22. A resultant mutant, named
as SAM-3, has considerable abilities to inhibit the growth of H22 and Hepa1-6 tumor cells in vitro and colon 26 solid tumor
in vivo. Furthermore, SAM-3 also exhibits significantly reduced toxicity compared with native SEC2. The study provides a novel
strategy for designing promising superantigen immunotherapeutic agent. The constructed SEC2 mutant SAM-3 can be used as a
powerful candidate for cancer immunotherapy and could compensate the deficiency caused by toxicity of native SEC2 in clinic. 相似文献
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The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed. 相似文献
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Donald H. Atha Amber Nagy Andrea Steinbrück Allison M. Dennis Jennifer A. Hollingsworth Varsha Dua Rashi Iyer Bryant C. Nelson 《Journal of nanobiotechnology》2017,15(1):79