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At least 289 records · Page 16Linked to original sources
PubMed2024

Chemical approaches to probe and engineer AAV vectors.

Adeno-associated virus (AAV) has emerged as the most promising vector for in vivo human gene therapy, with several therapeutic approvals in the last few years and countless more under development. Underlying this remarkable success are several attractive features that AAV offers, including lack of pathogenicity, low immunogenicity, long-term gene expression without genomic integration, the ability to infect both dividing and non-dividing cells, etc. However, the commonly used wild-type AAV capsids in therapeutic development present significant challenges, including inadequate tissue specificity and the need for large doses to attain therapeutic effectiveness, raising safety concerns. Additionally, significant preexisting adaptive immunity against most natural capsids, and the development of such anti-capsid immunity after the first treatment, represent major challenges. Strategies to engineer the AAV capsid are critically needed to address these challenges and unlock the full promise of AAV gene therapy. Chemical modification of the AAV capsid has recently emerged as a powerful new approach to engineer its properties. Unlike genetic strategies, which can be more disruptive to the delicate capsid assembly and packaging processes, "late-stage" chemical modification of the assembled capsid-whether at natural amino acid residues or site-specifically installed noncanonical amino acid residues-often enables a versatile approach to introducing new properties to the capsid. This review summarizes the significant recent progress in AAV capsid engineering strategies, with a particular focus on chemical modifications in advancing the next generation of AAV-based gene therapies.

Dependovirus↗
PubMed2003

Biochemical engineering: cues from cells.

Engineering principles are used in the exploitation of biocatalysts derived from cells. The purity of reagents, catalysts and maintenance of operation variables are extremely important for bioengineering systems. Any change in the purity of reagents or in operation variables usually leads to a dramatic decrease in productivity. Cellular systems, however, are able to work with relatively high impure conditions and increase their productivity in response to external signals. Thus the seemingly disordered 'bag of juice' or cytoplasm has more order and much higher order of integration than first appears. Learning the semantics of this paradoxical ability of order and integration would help bioengineers to understand and enhance productivity even using impure reagents.

Biomedical Engineering↗
PubMed2005

Chemical synthesis approaches to the engineering of ion channels.

Chemoselective ligation strategies have previously provided synthetic access to water-soluble proteins with novel properties, and more recently these strategies have been used to prepare ion channels. Examples of ion channels prepared by total chemical synthesis include bacterial mechanosensitive channels, and viral ion channels. Chemical protein synthesis allows for the generation of ion channel proteins with both native, and engineered structural or conductance properties.

Animals↗
PubMed2006

Progress in designing nucleic acid structures and fine-tuning their interactions.

The prediction of the structure of biological macromolecules at the atomic level and the design of new meta-stable structures and secondary interactions are critical tests of our understanding of the structures and the inter-atomic forces that underlie molecular biology. The capacity to accurately predict and design new structures and interactions will allow us to create nucleic acid sequences that will fold in new and useful ways. Here, we present some results to demonstrate the progress we have made in designing and assembling new nucleic acid structures that will make an increasingly important contribution to biology and medicine. We call the reaction cycle that exemplifies our approach 'A handshake from a hairpin on the way to a double helix.'

Base Sequence↗
PubMed2005

Artificial metalloenzymes based on biotin-avidin technology for the enantioselective reduction of ketones by transfer hydrogenation.

Most physiological and biotechnological processes rely on molecular recognition between chiral (handed) molecules. Manmade homogeneous catalysts and enzymes offer complementary means for producing enantiopure (single-handed) compounds. As the subtle details that govern chiral discrimination are difficult to predict, improving the performance of such catalysts often relies on trial-and-error procedures. Homogeneous catalysts are optimized by chemical modification of the chiral environment around the metal center. Enzymes can be improved by modification of gene encoding the protein. Incorporation of a biotinylated organometallic catalyst into a host protein (avidin or streptavidin) affords versatile artificial metalloenzymes for the reduction of ketones by transfer hydrogenation. The boric acid.formate mixture was identified as a hydrogen source compatible with these artificial metalloenzymes. A combined chemo-genetic procedure allows us to optimize the activity and selectivity of these hybrid catalysts: up to 94% (R) enantiomeric excess for the reduction of p-methylacetophenone. These artificial metalloenzymes display features reminiscent of both homogeneous catalysts and enzymes.

Biotin↗
PubMed2005

Supervised enzyme network inference from the integration of genomic data and chemical information.

MOTIVATION: The metabolic network is an important biological network which relates enzyme proteins and chemical compounds. A large number of metabolic pathways remain unknown nowadays, and many enzymes are missing even in known metabolic pathways. There is, therefore, an incentive to develop methods to reconstruct the unknown parts of the metabolic network and to identify genes coding for missing enzymes. RESULTS: This paper presents new methods to infer enzyme networks from the integration of multiple genomic data and chemical information, in the framework of supervised graph inference. The originality of the methods is the introduction of chemical compatibility as a constraint for refining the network predicted by the network inference engine. The chemical compatibility between two enzymes is obtained automatically from the information encoded by their Enzyme Commission (EC) numbers. The proposed methods are tested and compared on their ability to infer the enzyme network of the yeast Saccharomyces cerevisiae from four datasets for enzymes with assigned EC numbers: gene expression data, protein localization data, phylogenetic profiles and chemical compatibility information. It is shown that the prediction accuracy of the network reconstruction consistently improves owing to the introduction of chemical constraints, the use of a supervised approach and the weighted integration of multiple datasets. Finally, we conduct a comprehensive prediction of a global enzyme network consisting of all enzyme candidate proteins of the yeast to obtain new biological findings. AVAILABILITY: Softwares are available upon request.

Algorithms↗
PubMed2005

Globally linearized control on diabatic continuous stirred tank reactor: a case study.

This paper focuses on the promise of globally linearized control (GLC) structure in the realm of strongly nonlinear reactor system control. The proposed nonlinear control strategy is comprised of: (i) an input-output linearizing state feedback law (transformer), (ii) a state observer, and (iii) an external linear controller. The synthesis of discrete-time GLC controller for single-input single-output diabatic continuous stirred tank reactor (DCSTR) has been studied first, followed by the synthesis of feedforward/feedback controller for the same reactor having dead time in process as well as in disturbance. Subsequently, the multivariable GLC structure has been designed and then applied on multi-input multi-output DCSTR system. The simulation study shows high quality performance of the derived nonlinear controllers. The better-performed GLC in conjunction with reduced-order observer has been compared with the conventional proportional integral controller on the example reactor and superior performance has been achieved by the proposed GLC control scheme.

Algorithms↗
PubMed2001

Cysteine mutants as chemical sensors for ligand-receptor interactions.

The incorporation of cysteine residues into membrane receptors by mutagenesis has enabled the development of engineered proteins. Chemical modification of the mutant receptor using a wide range of biochemical and biophysical probes has facilitated functional studies of ligand-receptor interactions. In particular, the substituted-cysteine accessibility method (SCAM) represents a successful example of how to probe transmembrane receptor domains after chemical modification of the mutants with sulfydryl-reacting molecules. We propose an extension of this methodology using site-specific affinity probes that react with cysteine mutants to gain reliable structural information on the binding of a ligand in its receptor site.

Affinity Labels↗
PubMed2005

Stable biomimetic super-hydrophobic engineering materials.

We describe a simple and inexpensive method to produce super-hydrophobic surfaces on aluminum and its alloy by oxidation and chemical modification. Water or aqueous solutions (pH = 1-14) have contact angles of 168 +/- 2 and 161 +/- 2 degrees on the treated surfaces of Al and Al alloy, respectively. The super-hydrophobic surfaces are produced by the cooperation of binary structures at micro- and nanometer scales, thus reducing the energies of the surfaces. Such super-hydrophobic properties will greatly extend the applications of aluminum and its alloy as lubricating materials.

Aluminum↗
PubMed2005

Sonochemistry in environmental remediation. 1. Combinative and hybrid sonophotochemical oxidation processes for the treatment of pollutants in water.

Sonoprocessing is the utilization of sonic and ultrasonic waves in chemical synthesis and processes. It is a new and rapidly growing research field with broad applications in environmental engineering, green chemical synthesis, and processing. The application of this environmentally benign technique in environmental remediation is currently under active research and development. Sonochemical oxidation is effective in treating toxic effluents and reducing toxicity. However, the ultrasonic treatment is highly energy intensive since sonication is relatively inefficient with respect to total input energy and is therefore not economically attractive or feasible alone. Hence, sonochemistry has not yet received much attention as an alternative for industrial and large-scale chemical and environmental processes. One of the most interesting topics in the recent advances in sonochemistry is the possibility of double or more excitations with ultrasound and other types of energy. The coupling of ultrasound with other free energy sources (i.e., UV) or chemical oxidation utilizing H2O2, O3, or ferrous ion presents interesting and attractive approaches. Therefore, many recent efforts have been devoted to improving the efficiency of sonochemical reactions by exploiting the advantages of combinative or hybrid processes involving the simultaneous or sequential use of ultrasonic irradiation and other advanced oxidation processes, electrochemical processes, and biological treatment. This paper provides a critical review of the applications of ultrasound in environmental remediation, focusing on recent developments and unifying analysis of combinative or hybrid systems, namely, sonophotochemical oxidation processes.

Hot Temperature↗