scholarly journals Adeno-associated virus (AAV) vectors: Rational design strategies for capsid engineering

2018 ◽  
Vol 7 ◽  
pp. 58-63 ◽  
Author(s):  
Esther J. Lee ◽  
Caitlin M. Guenther ◽  
Junghae Suh
Keyword(s):  
Rational Design ◽  
Design Strategies ◽  
Adeno Associated Virus

scholarly journals Next Step in Gene Delivery: Modern Approaches and Further Perspectives of AAV Tropism Modification

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 750
Author(s):  
Maxim A. Korneyenkov ◽  
Andrey A. Zamyatnin
Keyword(s):  
Gene Therapy ◽  
Genome Organization ◽  
Rational Design ◽  
Structural Data ◽  
Rational Approach ◽  
Tissue Tropism ◽  
Adeno Associated Virus ◽  
Chemical Conjugation ◽  
The Usa ◽  
Therapy Delivery

Today, adeno-associated virus (AAV) is an extremely popular choice for gene therapy delivery. The safety profile and simplicity of the genome organization are the decisive advantages which allow us to claim that AAV is currently among the most promising vectors. Several drugs based on AAV have been approved in the USA and Europe, but AAV serotypes’ unspecific tissue tropism is still a serious limitation. In recent decades, several techniques have been developed to overcome this barrier, such as the rational design, directed evolution and chemical conjugation of targeting molecules with a capsid. Today, all of the abovementioned approaches confer the possibility to produce AAV capsids with tailored tropism, but recent data indicate that a better understanding of AAV biology and the growth of structural data may theoretically constitute a rational approach to most effectively produce highly selective and targeted AAV capsids. However, while we are still far from this goal, other approaches are still in play, despite their drawbacks and limitations.

scholarly journals Polymeric micelles and molecular modeling applied to the development of radiopharmaceuticals

2012 ◽  
Vol 48 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Sibila Roberta Marques Grallert ◽  
Carlota de Oliveira Rangel-Yagui ◽  
Kerly Fernanda Mesquita Pasqualoto ◽  
Leoberto Costa Tavares
Keyword(s):  
Molecular Modeling ◽  
Rational Design ◽  
Polymeric Micelles ◽  
Single Photon ◽  
Photon Emission ◽  
Disease Process ◽  
Diagnostic Techniques ◽  
Emission Computed Tomography ◽  
Amphiphilic Copolymers ◽  
Design Strategies

Micelles composed of amphiphilic copolymers linked to a radioactive element are used in nuclear medicine predominantly as a diagnostic application. A relevant advantage of polymeric micelles in aqueous solution is their resulting particle size, which can vary from 10 to 100 nm in diameter. In this review, polymeric micelles labeled with radioisotopes including technetium (99mTc) and indium (111In), and their clinical applications for several diagnostic techniques, such as single photon emission computed tomography (SPECT), gamma-scintigraphy, and nuclear magnetic resonance (NMR), were discussed. Also, micelle use primarily for the diagnosis of lymphatic ducts and sentinel lymph nodes received special attention. Notably, the employment of these diagnostic techniques can be considered a significant tool for functionally exploring body systems as well as investigating molecular pathways involved in the disease process. The use of molecular modeling methodologies and computer-aided drug design strategies can also yield valuable information for the rational design and development of novel radiopharmaceuticals.

scholarly journals Research fronts of Chemical Biology

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shanshan Lv
Keyword(s):  
High Throughput Screening ◽  
Drug Targets ◽  
Chemical Biology ◽  
Rational Design ◽  
Future Research ◽  
Design Strategies ◽  
Binding Assays ◽  
Cellular Mechanisms ◽  
Diagnostic Technologies

Abstract Over the past decades, researchers have witnessed substantially increasing and ever-growing interests and efforts in Chemical Biology studies, thanks to the development of genome and epi-genome sequencing (revealing potential drug targets), synthetic chemistry (producing new medicines), bioorthogonal chemistry (chemistry in living systems) and high-throughput screening technologies (in vitro cell systems, protein binding assays and phenotypic assays). This report presents literature search results for current research in Chemical Biology, to explore basic principles, summarize recent advances, identify key challenges, and provide suggestions for future research (with a focus on Chemical Biology in the context of human health and diseases). Chemical Biology research can positively contribute to delivering a better understanding of the molecular and cellular mechanisms that accompany pathology underlying diseases, as well as developing improved methods for diagnosis, drug discovery, and therapeutic delivery. While much progress has been made, as shown in this report, there are still further needs and opportunities. For instance, pressing challenges still exist in selecting appropriate targets in biological systems and adopting more rational design strategies for the development of innovative and sustainable diagnostic technologies and medical treatments. Therefore, more than ever, researchers from different disciplines need to collaborate to address the challenges in Chemical Biology.

scholarly journals Pathogenic Viruses Commonly Present in the Oral Cavity and Relevant Antiviral Compounds Derived from Natural Products

Medicines ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 120 ◽  
Author(s):  
Daisuke Asai ◽  
Hideki Nakashima
Keyword(s):  
Natural Products ◽  
Oral Cavity ◽  
Rational Design ◽  
Large Scale ◽  
Antiviral Agents ◽  
Marine Sponges ◽  
Design Strategies ◽  
Screening Programs ◽  
Human Oral Cavity ◽  
Antiviral Compounds

Many viruses, such as human herpesviruses, may be present in the human oral cavity, but most are usually asymptomatic. However, if individuals become immunocompromised by age, illness, or as a side effect of therapy, these dormant viruses can be activated and produce a variety of pathological changes in the oral mucosa. Unfortunately, available treatments for viral infectious diseases are limited, because (1) there are diseases for which no treatment is available; (2) drug-resistant strains of virus may appear; (3) incomplete eradication of virus may lead to recurrence. Rational design strategies are widely used to optimize the potency and selectivity of drug candidates, but discovery of leads for new antiviral agents, especially leads with novel structures, still relies mostly on large-scale screening programs, and many hits are found among natural products, such as extracts of marine sponges, sea algae, plants, and arthropods. Here, we review representative viruses found in the human oral cavity and their effects, together with relevant antiviral compounds derived from natural products. We also highlight some recent emerging pharmaceutical technologies with potential to deliver antivirals more effectively for disease prevention and therapy.

Lanthanide Doped Complexes and Organometallic Clusters: Design Strategies and their Applications in Biology and Photonics

2019 ◽  
Vol 9 (3) ◽  
pp. 166-217 ◽  
Author(s):  
Gangadharan A. Kumar
Keyword(s):  
Nanostructured Materials ◽  
Rational Design ◽  
Near Infrared ◽  
Organic Ligand ◽  
Central Core ◽  
Design Strategies ◽  
Ceramic Core ◽  
Light Emitting ◽  
Potential Applications ◽  
Lanthanide Atoms

In this review, we discuss the rational design of a new class of lanthanide-doped organometallic nanostructured materials called `molecular minerals`. Molecular minerals are nanostructured materials with a ceramic core made from chalcogenide groups and other heavy metals. Part of the central core atoms is replaced by suitable lanthanide atoms to impart fluorescent spectral properties. The ceramic core is surrounded by various types of organic networks thus making the structure partly ceramic and organic. The central core has superior optical properties and the surrounding organic ligand makes it easy to dissolve several kinds of organic solvents and fluoropolymers to make several kinds of active and passive photonic devices. This chapter starts with elaborate design strategies of lanthanidebased near-infrared emitting materials followed by the experimental results of selected near-infrared emitting lanthanide clusters. Finally, their potential applications in telecommunication, light-emitting diodes and medical imaging are discussed.

scholarly journals The Rational Design and Biological Mechanisms of Nanoradiosensitizers

Nanomaterials ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 504 ◽  
Author(s):  
Hainan Sun ◽  
Xiaoling Wang ◽  
Shumei Zhai
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Dna Damage ◽  
Rational Design ◽  
Design Strategies ◽  
Biological Mechanisms ◽  
Normal Tissues ◽  
Current State

Radiotherapy (RT) has been widely used for cancer treatment. However, the intrinsic drawbacks of RT, such as radiotoxicity in normal tissues and tumor radioresistance, promoted the development of radiosensitizers. To date, various kinds of nanoparticles have been found to act as radiosensitizers in cancer radiotherapy. This review focuses on the current state of nanoradiosensitizers, especially the related biological mechanisms, and the key design strategies for generating nanoradiosensitizers. The regulation of oxidative stress, DNA damage, the cell cycle, autophagy and apoptosis by nanoradiosensitizers in vitro and in vivo is highlighted, which may guide the rational design of therapeutics for tumor radiosensitization.

ChemInform Abstract: Rational Design Strategies for Industrial Catalysts

ChemInform ◽  
2010 ◽  
Vol 41 (46) ◽  
pp. no-no
Author(s):  
Saeed Alerasool ◽  
C. P. Kelkar ◽  
Robert J. Farrauto
Keyword(s):  
Rational Design ◽  
Design Strategies

Directed Evolution of Immune-Escaping Adeno-Associated Virus Vectors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3532-3532
Author(s):  
Stephan Maersch ◽  
Anke Huber ◽  
Michael Hallek ◽  
Hildegard Buening ◽  
Luca Perabo
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gene Transfer ◽  
Directed Evolution ◽  
Neutralizing Antibodies ◽  
Rational Design ◽  
Multiple Point ◽  
Repeated Treatment ◽  
Therapeutic Gene ◽  
Adeno Associated Virus

Abstract Efficiency of therapeutic gene transfer by adeno-associated virus of serotype 2 (AAV-2) vectors is hampered in patients with pre-existing immunity against the natural virus. Genetic engineering by rational design or directed evolution has been employed in the last 3 years to generate capsids that escape antibody neutralization and has led to identify several amino acid residues of the capsid proteins that can be mutated in order to decrease antibody recognition (Perabo et al., 2006; Maheshri et al, 2006; Lochrie et al., 2006). In this novel study, we aimed to exploit the comprehensive knowledge gathered so far by generating novel capsid variants that carried multiple point mutations at these previously identified sites. Capsid libraries were generated by codon randomization of several immunogenic residues and screened to isolate mutants that most efficiently infected human cells despite the presence of anti-AAV2 neutralizing antibodies. Besides testing novel combinations of concomitant mutations at these sites, this approach allowed for the first time an exhaustive scanning of combinations of all 20 natural amino acids at each position. We identified several novel capsid mutants that remain highly infectious even when incubated with serum concentrations that completely neutralize wild type AAV2. Our results demonstrate that combining mutations at several sites it is possible to improve the immune-escaping ability of the capsid. In addition, we show that escaping ability and other biological characteristics of these mutants are strongly dependent on the type of amino acid substituted, demonstrating that an exact choice of substituted amino acids is essential to maximize stealth properties and minimize loss of packaging ability, particle stability and transduction efficacy. These vectors can be used for therapeutic gene transfer to patients with pre-existing immunity, or for repeated treatment after antibodies are generated upon first application.

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