Development of specialized carriers capable of delivering effective RNAi and siRNA gene therapy

2021 ◽  
Author(s):  
Moataz Dowaidar

New cationic carriers must be molecularly designed to enable selective RNAi and siRNA transport and administration. Because at some time, the carriers will have to be removed from the cells and perfused out of the body, sophisticated, temporarily controllable biodegradable carriers are necessary. This indicates that the degradation process must be well regulated and possibly in several steps to destroy the carrier in a controlled manner.Moreover, multifunctional cationic carriers must be molecularly designed to carry and steer two independent kinds of siRNAs delivered at two very different rates. This allows sequential treatment of some diseases. Nanosized carriers must be enhanced to provide sufficient stability for the therapeutic duration of the system. In addition, there is the recurring issue of cationic carrier toxicity to be addressed in the near future. Despite the courageous and robust field efforts, a lot of difficulties still need to be resolved.

Author(s):  
Prithiv K R Kumar

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 88
Author(s):  
Martin Aringer ◽  
Anne Erler

How the main components in systemic sclerosis—namely autoimmunity, vasculopathy, and fibrosis—fit together is still not sufficiently clear. However, vascular treatment options are well established, the body of evidence for the efficacy of immunomodulatory approaches is increasing, and now at least one hopeful substance that may directly interfere with fibrosis is being tested. Although we still wait for important breakthroughs, there is grounds for hope that better therapeutic options will be available in the near future.


Semiotica ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Daniel Alcaraz Carrión ◽  
Javier Valenzuela

Abstract This study investigates whether there is a relation between the semantics of linguistic expressions that indicate temporal distance and the spatial properties of their co-speech gestures. To this date, research on time gestures has focused on features such as gesture axis, direction, and shape. Here we focus on a gesture property that has been overlooked so far: the distance of the gesture in relation to the body. To achieve this, we investigate two types of temporal linguistic expressions are addressed: proximal (e.g., near future, near past) and distal (e.g., distant past, distant future). Data was obtained through the NewsScape library, a multimodal corpus of television news. A total of 121 co-speech gestures were collected and divided into the two categories. The gestures were later annotated in terms of gesture space and classified in three categories: (i) center, (ii) periphery, and (iii) extreme periphery. Our results suggest that gesture and language are coherent in the expression of temporal distance: when speakers locate an event far from them, they tend to gesture further from their body; similarly, when locating an event close to them, they gesture closer to their body. These results thus reveal how co-speech gestures also reflect a space-time mapping in the dimension of distance.


2021 ◽  
Vol 1017 ◽  
pp. 21-30
Author(s):  
Victor Danilov ◽  
Arkady Ayzenshtadt ◽  
Maria Frolova

This paper discusses the results of experimental studies on the selection of the repair mixture compound for recreating the surface layer of the historical brick of the 18th century architectural monument “Commercial Bank” in Arkhangelsk. According to the research results, it was found that the historical brick has a relatively higher density and increased calcium content than the modern one. The characteristics of the surfaces of the analyzed materials based on the component indicators of specific surface energy showed that the brick of 1859, characterized by the highest degree of destruction, has the maximum value of the polar energy component. This fact may indicate a greater hydrophilicity of the surface in relation to atmospheric water and, as a result, a more intensive degradation process. It is established that the composition of the repair mixture with the addition of brick crumbs in the amount of 50 % has a value of the polar part of the surface tension equal to similar parameters for historical bricks (1786 and 1859) after their preliminary priming. The use of this mixture to recreate the surface layer of the brick will allow atmospheric water to pass freely through the repair compound and the body of the brick, without concentrating on the interface and without causing its destruction and detachment when drying.


2013 ◽  
Vol 373-375 ◽  
pp. 552-557
Author(s):  
Wei Dong Song ◽  
Gao Feng Liang ◽  
Xiao Li Yang ◽  
Xiao Wei Son ◽  
Jing Yu Guo ◽  
...  

Medical ultrasonic B-scans often suffer from intensity inhomogeneities that originates from the nonuniform attenuation properties of the sonic beam within the body. In order to correct signal attenuation in the tissue, time gain compensation (TGC) is routinely used in medical ultrasound scanners. However, TGC assumes a uniform attenuation coefficient for all body tissues. Since this assumption is evidently inaccurate, over-amplification or under-amplification sometimes appear. This is a major problem for intensity-based, automatic segmentation of video-intensity images because conventional threshold-based or intensity-statistic-based approaches do not work well in the presence of such image distortions. The main contribution of this paper is that additional spatial image features are incorporated to improve inhomogeneity correction and to make it more dynamic besides most commonly used intensity features, so that local intensity variations can be corrected more efficiently. The degraded image is corrected by the inverse of the image degradation model. The image degradation process is described by a linear model, consisting of a multiplicative and an additive component which are modeled by a combination of smoothly varying basis functions. Spatial information about intensity nonuniformity is obtained using cubic spline smoothing and entropy minimizing. Gray-level histogram information of the image corrupted by intensity inhomogeneity is exploited from a signal processing perspective. We explain how this model can be related to the ultrasonic physics of image formation to justify our approach. Experiments are presented on synthetic images and real US data to evaluate quantitatively the accuracy of the method.


2003 ◽  
Vol 2003 (2) ◽  
pp. 110-137 ◽  
Author(s):  
Tracy Robson ◽  
David G. Hirst

Cancer gene therapy has been one of the most exciting areas of therapeutic research in the past decade. In this review, we discuss strategies to restrict transcription of transgenes to tumour cells. A range of promoters which are tissue-specific, tumour-specific, or inducible by exogenous agents are presented. Transcriptional targeting should prevent normal tissue toxicities associated with other cancer treatments, such as radiation and chemotherapy. In addition, the specificity of these strategies should provide improved targeting of metastatic tumours following systemic gene delivery. Rapid progress in the ability to specifically control transgenes will allow systemic gene delivery for cancer therapy to become a real possibility in the near future.


Science ◽  
2018 ◽  
Vol 359 (6372) ◽  
pp. eaan4672 ◽  
Author(s):  
Cynthia E. Dunbar ◽  
Katherine A. High ◽  
J. Keith Joung ◽  
Donald B. Kohn ◽  
Keiya Ozawa ◽  
...  

After almost 30 years of promise tempered by setbacks, gene therapies are rapidly becoming a critical component of the therapeutic armamentarium for a variety of inherited and acquired human diseases. Gene therapies for inherited immune disorders, hemophilia, eye and neurodegenerative disorders, and lymphoid cancers recently progressed to approved drug status in the United States and Europe, or are anticipated to receive approval in the near future. In this Review, we discuss milestones in the development of gene therapies, focusing on direct in vivo administration of viral vectors and adoptive transfer of genetically engineered T cells or hematopoietic stem cells. We also discuss emerging genome editing technologies that should further advance the scope and efficacy of gene therapy approaches.


2014 ◽  
Vol 13 (1) ◽  
pp. 135-144
Author(s):  
I. V. Mitrofanova ◽  
I. V. Milto ◽  
I. V. Suhodolo ◽  
G. Yu. Vasyukov

Nanomaterials  –  materials,  whouse  structure  elements  has  proportions  doesn’t  exceed  100  nm.  In superdispersed state matter acquire new properties. In the last decade, carbon nanotubes become the most popular nanomaterials, that cause attention of representatives of various scientific field. The сarbon nanotubes offer new opportunities for biological and medical applications: imaging at the molecular, cellular and tissue levels, biosensors and electrodes based on carbon nanotubes, target delivery of various substances, radiation and photothermal therapy. The most promising of carbon nanotubes in the context of biomedical applications is their ability to penetrate the various tissues of the body and carry large doses of agents, providing diagnostic and therapeutic effects. Functionalized nanotubes are biodegradable. Other current direction of using carbon nanotubes in medicine and biology is to visualize objects on the molecular, cellular and tissue level. Associated with carbon nanotubes contrasting substances improve the visualization of cells and tissues, which can detected new patterns of development of the pathological process. Due to the vagueness of the question of biocompatibility and cytotoxicity of carbon nanotubes possibility of their practical application is hampered. Before the introduction of carbon nanotubes into practical health care is necessary to provide all the possible consequences of using nanotubes. High rates of properties and development of new nanostructures based on carbon nanotubes in the near future will lead to new advances related to the application and development of new parameters that will determine their properties and effects. In these review attention is paid to the structure, physico-chemical properties of nanotubes, their functionalization, pharmacokinetics and pharmacodynamics and all aspects of using of carbon nanotubes.


Author(s):  
A. Dziaková ◽  
A. Valenčáková ◽  
E. Hatalová ◽  
J. Kalinová

Gene therapy is strategy based on using genes as pharmaceuticals. Gene therapy is a treatment that involves altering the genes inside body's cells to stop disease. Genes contain DNA- the code controlling body form and function. Genes that do not work properly can cause disease. Gene therapy replaces a faulty gene or adds a new gene in an attempt to cure disease or improve the ability of the body to fight disease. Gene therapy holds promise for treating a wide range of diseases, including cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Various types of genetic material are used in gene therapy; double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), plasmid DNA and antisense oligodeoxynucleotides (ASON). The success of gene therapy depends on assuring the entrance of the therapeutic gene to targeted cells without any form of biodegradation. Commonly used vectors in gene therapy are: adenoviruses (400 clinical studies; 23.8%), retroviruses (344 clinical studies; 20.5%), unenveloped/plasmid DNA (304 clinical studies, 17.7%), adenoassociated viruses (75 clinical studies; 4.5%) and others. In this paper, we have reviewed the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors.


2021 ◽  
Author(s):  
Moataz Dowaidar

The perspective of Anderson–Fabry disease (ADF) therapy is changing, and we should be ready to adapt to any new information. Today, ERT is still a viable therapeutic option for AFD patients. Chaperone therapy may be beneficial as a first-line treatment for adult patients with amenable mutations. In the near future, the PEGylate enzyme may be approved and added to our indications. SRT, gene therapy, and other enzyme preparations, such as moss alpha gal, are all still in the development phases.


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