scholarly journals Nonlinear Behaviors in Gene Therapy Theoretical and experimental aspects

2018 ◽  
Vol 55 (3) ◽  
pp. 340-343
Author(s):  
Gabriela Cioca ◽  
Mariana Pinteala ◽  
Elena Simona Bacaita ◽  
Iuliana Oprea ◽  
Irina Crumpei Tanasa ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Theoretical Model ◽  
Genetic Disorders ◽  
Fractal Theory ◽  
Genetic Material ◽  
Theoretical Models ◽  
Relativity Theory ◽  
Dna Release ◽  
Scale Relativity ◽  
Nonlinear Behaviors

Gene therapy represents a promising method for treating genetic disorders or diseases consisting in the transfer of genetic material (DNA) to cells in order to substitute or to slow down the evolution of the defective gene in cells. Theoretical models to predict DNA release are difficult to build in the classical approach of continuous and differentiable physical quantities, due to the high number of interdependent phenomena that occur simultaneous. The article presents a theoretical model based on the fractal theory of motions in the form of Scale Relativity Theory to describe nonlinear behaviors in gene therapy. Correlations of the theoretical model with experimental data are also observed.

Gene Therapy for Inherited Retinopathies: Update on Development Progress

2018 ◽  
Vol 2 (4) ◽  
pp. 219-226
Author(s):  
Susan Sun ◽  
Sandra R. Montezuma
Keyword(s):  
Gene Therapy ◽  
Genetic Disorders ◽  
Treatment Options ◽  
Genetic Material ◽  
Disease Process ◽  
Supportive Therapy ◽  
The Us ◽  
Retinal Disorders ◽  
The Status ◽  
Therapy Treatment

Inherited retinopathies are a group of genetic disorders that lead to blindness and/or vision impairment. Until now, treatment options for inherited retinopathies largely remained limited to supportive therapy. Gene therapy is an attractive therapeutic technique that allows repair of diseased genes, and it has shown success in vision improvement for patients affected by retinal disorders caused by genetic mutations. The US Food and Drug Administration approved the first gene therapy treatment for the eye, indicated for biallelic RPE65 mutation associated Leber congenital amaurosis (LCA), in December of 2017. Additionally, results from other ongoing clinical trials could further establish gene therapy as the milestone treatment that plays a role in disease process reversal for inherited retinopathies. This review article provides an update on the status of gene therapy for treatment of a variety of retinopathies, including LCA, choroideremia, achromatopsia, Stargardt disease, X-linked retinitis pigmentosa, and X-linked retinoschisis. Furthermore, this article explores transport methods of the genetic material, as well as therapy-delivery approaches used in the clinical setting.

scholarly journals Gene Therapy: The Molecular Bandage for Treating Genetic Disorders

1970 ◽  
Vol 3 (1) ◽  
pp. 24-27
Author(s):  
Md Manjurul Karim
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Genetic Disorders ◽  
Clinical Status ◽  
Genetic Material ◽  
Review Article ◽  
Cell Tissue ◽  
Efficient Gene ◽  
Effective Delivery ◽  
A Cell

The concept of gene therapy involves the transfer of genetic material into a cell, tissue, or whole organ, with a view to curing a disease or at least improving the clinical status of a patient. Much of its success relies heavily on the development of an effective delivery system that is capable of efficient gene transfer in a variety of tissues, without causing any associated pathogenic effects. Viral vectors currently offer the best choice for efficient gene delivery, what has been discussed in this review article. Their performance and pathogenecity has been evaluated in animal models, and encouraging results form the basis for clinical trials to treat genetic disorders and acquired diseases. Despite some initial success in these trials, vector development remains a seminal concern for improved gene therapy technologies. DOI: http://dx.doi.org/10.3329/akmmcj.v3i1.10110 AKMMCJ 2012; 3(1): 24-27

scholarly journals Assessment of Complex System Dynamics via Harmonic Mapping in a Multifractal Paradigm

Mathematics ◽  
2021 ◽  
Vol 9 (24) ◽  
pp. 3298
Author(s):  
Gabriel Gavriluț ◽  
Liliana Topliceanu ◽  
Manuela Gîrțu ◽  
Ana Maria Rotundu ◽  
Stefan Andrei Irimiciuc ◽  
...  
Keyword(s):  
Complex System ◽  
System Dynamics ◽  
Parallel Transport ◽  
Harmonic Mapping ◽  
Relativity Theory ◽  
Plasma Dynamics ◽  
Hidden Symmetry ◽  
Scale Relativity ◽  
Nonlinear Behaviors ◽  
Complex System Dynamics

In the present paper, nonlinear behaviors of complex system dynamics from a multifractal perspective of motion are analyzed. In the framework of scale relativity theory, by analyzing the dynamics of complex system entities based on continuous but non-differentiable curves (multifractal curves), both the Schrödinger and Madelung scenarios on the holographic implementations of dynamics are functional and complementary. In the Madelung scenario, the holographic implementation of dynamics (i.e., free of any external or internal constraints) has some important consequences explicated by means of various operational procedures. The selected procedures involve synchronous modes through SL (2R) transformation group based on a hidden symmetry, coherence domains through Riemann manifold embedded with a Poincaré metric based on a parallel transport of direction (in a Levi Civita sense). Other procedures used here relate to the stationary-non-stationary dynamics transition through harmonic mapping from the usual space to the hyperbolic one manifested as cellular and channel type self-structuring. Finally, the Madelung scenario on the holographic implementations of dynamics are discussed with respect to laser-produced plasma dynamics.

scholarly journals Multifractality through Non-Markovian Stochastic Processes in the Scale Relativity Theory. Acute Arterial Occlusions as Scale Transitions

Entropy ◽  
2021 ◽  
Vol 23 (4) ◽  
pp. 444
Author(s):  
Nicolae Dan Tesloianu ◽  
Lucian Dobreci ◽  
Vlad Ghizdovat ◽  
Andrei Zala ◽  
Adrian Valentin Cotirlet ◽  
...  
Keyword(s):  
Stochastic Processes ◽  
Standard Form ◽  
Momentum Conservation ◽  
Relativity Theory ◽  
Horizontal Pipe ◽  
Scale Transition ◽  
Theory Of Motion ◽  
Multifractal Theory ◽  
Scale Relativity ◽  
Specific Momentum

By assimilating biological systems, both structural and functional, into multifractal objects, their behavior can be described in the framework of the scale relativity theory, in any of its forms (standard form in Nottale’s sense and/or the form of the multifractal theory of motion). By operating in the context of the multifractal theory of motion, based on multifractalization through non-Markovian stochastic processes, the main results of Nottale’s theory can be generalized (specific momentum conservation laws, both at differentiable and non-differentiable resolution scales, specific momentum conservation law associated with the differentiable–non-differentiable scale transition, etc.). In such a context, all results are explicated through analyzing biological processes, such as acute arterial occlusions as scale transitions. Thus, we show through a biophysical multifractal model that the blocking of the lumen of a healthy artery can happen as a result of the “stopping effect” associated with the differentiable-non-differentiable scale transition. We consider that blood entities move on continuous but non-differentiable (multifractal) curves. We determine the biophysical parameters that characterize the blood flow as a Bingham-type rheological fluid through a normal arterial structure assimilated with a horizontal “pipe” with circular symmetry. Our model has been validated based on experimental clinical data.

scholarly journals How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

2021 ◽  
Vol 22 (14) ◽  
pp. 7545
Author(s):  
Myriam Sainz-Ramos ◽  
Idoia Gallego ◽  
Ilia Villate-Beitia ◽  
Jon Zarate ◽  
Iván Maldonado ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Practice ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Viral Vector ◽  
Clinical Success ◽  
Genetic Material ◽  
Viral Gene ◽  
Promising Alternative ◽  
Vector Systems

Efficient delivery of genetic material into cells is a critical process to translate gene therapy into clinical practice. In this sense, the increased knowledge acquired during past years in the molecular biology and nanotechnology fields has contributed to the development of different kinds of non-viral vector systems as a promising alternative to virus-based gene delivery counterparts. Consequently, the development of non-viral vectors has gained attention, and nowadays, gene delivery mediated by these systems is considered as the cornerstone of modern gene therapy due to relevant advantages such as low toxicity, poor immunogenicity and high packing capacity. However, despite these relevant advantages, non-viral vectors have been poorly translated into clinical success. This review addresses some critical issues that need to be considered for clinical practice application of non-viral vectors in mainstream medicine, such as efficiency, biocompatibility, long-lasting effect, route of administration, design of experimental condition or commercialization process. In addition, potential strategies for overcoming main hurdles are also addressed. Overall, this review aims to raise awareness among the scientific community and help researchers gain knowledge in the design of safe and efficient non-viral gene delivery systems for clinical applications to progress in the gene therapy field.

scholarly journals Characterization of Recombinant Adeno-Associated Viruses (rAAVs) for Gene Therapy Using Orthogonal Techniques

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 586
Author(s):  
Liam Cole ◽  
Diogo Fernandes ◽  
Maryam T. Hussain ◽  
Michael Kaszuba ◽  
John Stenson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Light Scattering ◽  
Dynamic Light Scattering ◽  
Viral Vector ◽  
Structural Characteristics ◽  
Genetic Material ◽  
Label Free ◽  
Gene Therapies ◽  
Multiple Challenges

Viruses are increasingly used as vectors for delivery of genetic material for gene therapy and vaccine applications. Recombinant adeno-associated viruses (rAAVs) are a class of viral vector that is being investigated intensively in the development of gene therapies. To develop efficient rAAV therapies produced through controlled and economical manufacturing processes, multiple challenges need to be addressed starting from viral capsid design through identification of optimal process and formulation conditions to comprehensive quality control. Addressing these challenges requires fit-for-purpose analytics for extensive characterization of rAAV samples including measurements of capsid or particle titer, percentage of full rAAV particles, particle size, aggregate formation, thermal stability, genome release, and capsid charge, all of which may impact critical quality attributes of the final product. Importantly, there is a need for rapid analytical solutions not relying on the use of dedicated reagents and costly reference standards. In this study, we evaluate the capabilities of dynamic light scattering, multiangle dynamic light scattering, and SEC–MALS for analyses of rAAV5 samples in a broad range of viral concentrations (titers) at different levels of genome loading, sample heterogeneity, and sample conditions. The study shows that DLS and MADLS® can be used to determine the size of full and empty rAAV5 (27 ± 0.3 and 33 ± 0.4 nm, respectively). A linear range for rAAV5 size and titer determination with MADLS was established to be 4.4 × 1011–8.7 × 1013 cp/mL for the nominally full rAAV5 samples and 3.4 × 1011–7 × 1013 cp/mL for the nominally empty rAAV5 samples with 3–8% and 10–37% CV for the full and empty rAAV5 samples, respectively. The structural stability and viral load release were also inferred from a combination of DLS, SEC–MALS, and DSC. The structural characteristics of the rAAV5 start to change from 40 °C onward, with increasing aggregation observed. With this study, we explored and demonstrated the applicability and value of orthogonal and complementary label-free technologies for enhanced serotype-independent characterization of key properties and stability profiles of rAAV5 samples.

Investigation on penetration model of shaped charge jet in water

2016 ◽  
Vol 30 (02) ◽  
pp. 1550268 ◽  
Author(s):  
Jinwei Shi ◽  
Xingbai Luo ◽  
Jinming Li ◽  
Jianwei Jiang
Keyword(s):  
Numerical Simulation ◽  
Theoretical Model ◽  
Model Simulation ◽  
Theoretical Models ◽  
Theoretical Research ◽  
Water Medium ◽  
Simulation Results ◽  
Jet Penetration ◽  
The Impact ◽  
Penetration Velocity

To analyze the process of jet penetration in water medium quantitatively, the properties of jet penetration spaced target with water interlayer were studied through test and numerical simulation. Two theoretical models of jet penetration in water were proposed. The theoretical model 1 was established considering the impact of the shock wave, combined with the shock equation Rankine–Hugoniot and the virtual origin calculation method. The theoretical model 2 was obtained by fitting theoretical analysis and numerical simulation results. The effectiveness and universality of the two theoretical models were compared through the numerical simulation results. Both the models can reflect the relationship between the penetration velocity and the penetration distance in water well, and both the deviation and stability of theoretical model 1 are better than 2, the lower penetration velocity, and the larger deviation of the theoretical model 2. Therefore, the theoretical model 1 can reflect the properties of jet penetration in water effectively, and provide the reference of model simulation and theoretical research.

Nonlinear Analysis of L-shaped Pipe Conveying Fluid with the Aid of Absolute Nodal Coordinate Formulation

2021 ◽  
Author(s):  
K. Zhou ◽  
H.R. Yi ◽  
Huliang Dai ◽  
H Yan ◽  
Z.L. Guo ◽  
...  
Keyword(s):  
Theoretical Model ◽  
Flow Velocity ◽  
Absolute Nodal Coordinate Formulation ◽  
Strong Relationship ◽  
Excitation Amplitude ◽  
Pipe Conveying Fluid ◽  
Base Excitation ◽  
Absolute Nodal Coordinate ◽  
Nonlinear Behaviors ◽  
Conveying Fluid

Abstract By adopting the absolute nodal coordinate formulation, a novel and general nonlinear theoretical model, which can be applied to solve the dynamics of combined straight-curved fluid-conveying pipes with arbitrary initially configurations and any boundary conditions, is developed in the current study. Based on this established model, the nonlinear behaviors of the cantilevered L-shaped pipe conveying fluid with and without base excitations are systematically investigated. Before starting the research, the developed theoretical model is verified by performing three validation examples. Then, with the aid of this model, the static deformations, linear stability, and nonlinear self-excited vibrations of the L-shaped pipe without the base excitation are determined. It is found that the cantilevered L-shaped pipe suffers from the static deformations when the flow velocity is subcritical, and will undergo the limit-cycle motions as the flow velocity exceeds the critical value. Subsequently, the nonlinear forced vibrations of the pipe with a base excitation are explored. It is indicated that the period-n, quasi-periodic and chaotic responses can be detected for the L-shaped pipe, which has a strong relationship with the flow velocity, excitation amplitude and frequency.

Potential strategies for cancer gene therapy

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Clinical Stage ◽  
Genetic Material ◽  
Direct Methods ◽  
Cancer Gene Therapy ◽  
Target Cells ◽  
Target Tissue ◽  
Cancer Gene ◽  
P Gene

Gene therapy involves transferring genetic material (DNA or RNA) to repair, regulate or replace genes to cure a disease. One of the most crucial barriers is successful delivery of the targeted gene into the target tissue. Various vector-based approaches have been developed to deliver the transgene to the target cells. In different cancers, numerous of these vectors are being developed for purposes such as immunotherapy, suicide gene therapy, microRNA (miRNA) focused treatment, oncogene silencing, and gene editing using CRISPR/Cas9. This article reviews several alternatives to cancer gene therapy, as well as their preclinical and clinical outcomes, possible limitations, and overall therapy effects. Ways of delivering cancer gene therapy include direct methods for introducing genetic material. Nonviral vectors are easy to manufacture and may be chemically modified to increase their usefulness. Cationic polymers such as Poly-L-Lysine (PLL) and Polyethylenimine (PEI-SS) are the most extensively used polycationic polymers for gene transfer, particularly in vitro. Many RNAi-based therapeutic approaches are approaching the clinical stage, and nanocarriers are likely to play a crucial role in treating specific cancers. In the previous decade, non-viral approaches were used in more than 17 percent of all gene therapy trials. The message is that this is a safe and effective technique for transferring genes to cancer patients who need it to be a safe, successful therapy. Exosomes were developed to carry oncogene-specific short interfering RNA. Sushrut and colleagues revealed that exosomes provide superior carriers of short RNA and prevent tumor growth than liposomes. Inhalation-based gene therapy (aerosol-mediated gene delivery) has gained pace as a feasible treatment approach, especially for lung cancer. Because the intended transgene is steered to specific cells/tissues, this should further increase therapeutic efficiency.

scholarly journals Gene Therapy in the Management of Erectile Dysfunction (ED): Past, Present, and Future

2009 ◽  
Vol 9 ◽  
pp. 846-854 ◽  
Author(s):  
Arnold Melman ◽  
Kelvin P. Davies
Keyword(s):  
Gene Therapy ◽  
Erectile Dysfunction ◽  
Viral Vectors ◽  
Genetic Material ◽  
Phase I Trials ◽  
Clinical Phase ◽  
The Past ◽  
Novel Treatment ◽  
Therapy Treatment ◽  
Gene Transfer Techniques

In the past, many researchers considered viral vectors to be the most promising candidates to transfer genetic material into the corpora for the treatment of erectile dysfunction. However, at present, no viral vectors have progressed to human trials. In contrast, the use of naked gene therapy, a plasmid expressing the human Maxi-K potassium channel, is the only gene therapy treatment to be evaluated in clinical phase I trials to date. The success of these studies, proving the safety of this treatment, has paved the way for the development of future gene transfer techniques based on similar transfer methods, as well as novel treatment vectors, such as stem cell transfer.

Sign in / Sign up

Export Citation Format

Share Document