scholarly journals GENE THERAPY FOR OBSTETRIC CONDITIONS

2014 ◽  
Vol 25 (3-4) ◽  
pp. 147-177
Author(s):  
REBECCA N. SPENCER ◽  
DAVID J. CARR ◽  
ANNA L. DAVID
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Lipoprotein Lipase ◽  
Molecular Mechanisms ◽  
Viral Vector ◽  
Genetic Disorders ◽  
Genetic Diseases ◽  
Nasopharyngeal Cancer ◽  
New Paradigm ◽  
Gene Therapies

The first clinical trials of gene therapy in the 1990s offered the promise of a new paradigm for the treatment of genetic diseases. Over the decades that followed the challenges and setbacks which gene therapy faced often overshadowed any successes. Despite this, recent years have seen cause for renewed optimism. In 2012 Glybera™, an adeno-associated viral vector expressing lipoprotein lipase, became the first gene therapy product to receive marketing authorisation in Europe, with a licence to treat familial lipoprotein lipase deficiency. This followed the earlier licensing in China of two gene therapies: Gendicine™ for head and neck squamous cell carcinoma and Oncorine™ for late-stage nasopharyngeal cancer. By this stage over 1800 clinical trials had been, or were being, conducted worldwide, and the therapeutic targets had expanded far beyond purely genetic disorders. So far no trials of gene therapy have been carried out in pregnancy, but an increasing understanding of the molecular mechanisms underlying obstetric diseases means that it is likely to have a role to play in the future. This review will discuss how gene therapy works, its potential application in obstetric conditions and the risks and limitations associated with its use in this setting. It will also address the ethical and regulatory issues that will be faced by any potential clinical trial of gene therapy during pregnancy.

Cardiac disease: Current approaches to gene therapy

2020 ◽  
pp. 62-75
Author(s):  
Reyad ul-ferdous ◽  
◽  
Shofiul Azam ◽  
◽  
◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Gene Delivery ◽  
Cardiac Disease ◽  
Target Genes ◽  
Viral Vector ◽  
Delivery Methods ◽  
Gene Therapies ◽  
Inherited Cardiomyopathies

Background: Last decade over the world, the cardiac disease becomes a leading cause of death. Gene-based therapies become a promising treatment for patients affected by cardiovascular diseases, such as myocardial infarction (MI), arteriosclerosis, heart failure and so on, but also underline the require for reproducible results in preclinical and clinical studies for efficacy and safety. Aim: This book chapter describes the current research prospect of gene therapy for cardiac disease. We focus on the various models to deliver genes using viral, non-viral vector, delivery methods, targets gene, recent clinical trials, inherited cardiomyopathies target genes and Present advances of CRISPR/Cas 9 for cardiovascular gene therapy. We recapitulate some challenges that require being overcome, future directions of gene therapies for cardiac disease. Materials and Methods: All required information regards Lef-7 was generated by exploring the internet search engine like as (PubMed, Wiley, ScienceDirect, CNKI, ACS, Google Scholar, Web of Science, SciFinder, and Baidu Scholar) and libraries. Results: In this book chapter, we focus on the present prospect of gene targets, gene delivery methods, and efficient vector to deliver gene, targets gene, recent clinical trials, inherited cardiomyopathies target genes and present advances of CRISPR/Cas 9 technology for the treatment of cardiac disease using gene therapy. Recent clinical trials require modifying vectors and gene delivery approaches to achieve effective results for cardiac gene therapy. Conclusion: In this book chapter, we integrate a historical perspective with recent advances that will likely affect clinical development in this research area.

scholarly journals Gene therapies and COVID-19 vaccines: a necessary discussion in relation with viral vector-based approaches

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Angel Aledo-Serrano ◽  
Antonio Gil-Nagel ◽  
Julian Isla ◽  
Ana Mingorance ◽  
Fernando Mendez-Hermida ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Vaccine Development ◽  
Viral Vector ◽  
Genetic Disorders ◽  
Genetic Diseases ◽  
Cross Reactivity ◽  
Medical Community ◽  
Gene Therapies ◽  
Satisfactory Answer ◽  
The Right

AbstractThe COVID-19 pandemic is adding an unanticipated concern for those affected by genetic diseases. Most of the new treatment achievements for these patients are made possible as a result of advances in viral-based products. Among them, adenoviruses (AdV) and especially adeno-associated viruses (AAV) are important players. The concerns and the conversation around this issue have increased as COVID-19 vaccines approach the market. What if the viral vectors become the mainstream strategy for vaccine development? Will the immune response elicited against the vector compromise the efficacy of future gene therapies? Patients with genetic diseases and patient advocacy groups are requesting information to the medical community about the potential impact of these vaccines in future gene therapy treatments, and physicians and scientists are not able to provide satisfactory answer yet. Importantly, the frequency of cross-reactivity among different AAV serotypes can be as high as 50%. This would have potential implications for patients with genetic disorders who could benefit from gene therapies, often coming in the form of AAV-based gene therapies. As in many other aspects, this pandemic is challenging our capacity to coordinate, plan ahead and align different medical objectives. In this case, having such conversation early on might allow us to make the right choices while we are still on time.

scholarly journals Do fair and just systems require compensation for the disadvantages of the natural lottery? a discussion on society's duties on the provision of gene therapy

2019 ◽  
Vol 22 (1) ◽  
pp. 69-74
Author(s):  
PE Ekmekci ◽  
MD Güner
Keyword(s):  
Gene Therapy ◽  
Genetic Disease ◽  
Equal Opportunity ◽  
Genetic Disorders ◽  
Genetic Diseases ◽  
Medical Science ◽  
Main Question ◽  
Treatment Needs ◽  
Gene Therapies ◽  
Recent Advances

AbstractGenetic diseases have been thought to be acquired as a result of sheer bad luck. However, recent advances in medical science have demonstrated the mechanisms of genetic disorders, which enable us to intervene with their occurrence and treatment. Today, gene therapy, once considered too risky, has become safer and can save the lives of patients with previously untreatable and lethal genetic diseases. However, the positive expectations from gene therapy are overshadowed by their extremely high prices. Thus, the duty of society in the provision of gene therapies has been frequently discussed. The discussions mainly focus on how to meet the genetic treatment needs of patients without violating the notion of justice and fairness in society. This study discusses the theoretical grounds for society's duty to compensate for genetic disease patients' disadvantages by providing them with appropriate genetic treatment. The main question is whether a fair and just system requires society to provide available lifesaving gene therapy to patients in need. The discussion is constructed on the crucial notion of the fair equal opportunity principle in a just system and the plausibility of including disadvantages emerging from bad luck in the natural lottery in the domain of justice.

scholarly journals The Ocular Gene Delivery Landscape

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1135
Author(s):  
Bhubanananda Sahu ◽  
Isha Chug ◽  
Hemant Khanna
Keyword(s):  
Gene Therapy ◽  
Genetic Diseases ◽  
Gene Therapies ◽  
Advantages And Disadvantages ◽  
Fda Approval ◽  
New Information ◽  
Efficient Delivery ◽  
Delivery Routes ◽  
History Of ◽  
Different Parts

The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness, numerous studies have been initiated to develop gene therapies for other forms of eye diseases. These examinations have revealed new information about the benefits as well as restrictions to using drug-delivery routes to the different parts of the eye. In this article, we will discuss a brief history of gene therapy and its importance to the eye and ocular delivery landscape that is currently being investigated, and provide insights into their advantages and disadvantages. Efficient delivery routes and vehicle are crucial for an effective, safe, and longer-lasting therapy.

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.

scholarly journals Critical Aspects of Clinical Trial Design for Novel Cell and Gene Therapies

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Zinovia Kefalopoulou ◽  
Iciar Aviles-Olmos ◽  
Thomas Foltynie
Keyword(s):  
Gene Therapy ◽  
Viral Vector ◽  
Safety Data ◽  
Clinical Trial Design ◽  
Open Label ◽  
Double Blind ◽  
Gene Therapies ◽  
Technological Advances ◽  
Vector Gene Transfer ◽  
Cell And Gene Therapy

Neural cell transplantation and gene therapy have attracted considerable interest as promising therapeutic alternatives for patients with Parkinson's disease (PD). Preclinical and open-label studies have suggested that grafted fetal neural tissue or viral vector gene transfer can achieve considerable biochemical and clinical improvements, whereas subsequent double-blind, placebo-controlled protocols have produced rather more modest and variable results. Detailed evaluation of these discordant findings has highlighted several crucial issues such as patient selection criteria, details surrounding transplantation or gene therapy methodologies, as well as the study designs themselves that ought to be carefully considered in the planning phases of future clinical trials. Beyond the provision of symptomatic efficacy and safety data, it also remains to be identified whether the possibilities offered by stem cell and gene therapy technological advances might translate to meaningful neuroprotection and/or disease-modifying effects or alleviate the nonmotor aspects of PD and thus offer additional benefits beyond those achieved through conventional pharmacotherapy or deep brain stimulation (DBS).

scholarly journals Nonclinical Studies that Support Viral Vector-Delivered Gene Therapies: An EFPIA Gene Therapy Working Group Perspective

2020 ◽  
Vol 19 ◽  
pp. 89-98
Author(s):  
Michael W. Bolt ◽  
Laurence O. Whiteley ◽  
Jessica L. Lynch ◽  
Brian Lauritzen ◽  
Antonio R. Fernández de Henestrosa ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Working Group ◽  
Viral Vector ◽  
Gene Therapies

scholarly journals Gene therapy for hemophilia: what does the future hold?

2018 ◽  
Vol 9 (9) ◽  
pp. 273-293 ◽  
Author(s):  
Bhavya S. Doshi ◽  
Valder R. Arruda
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Neutralizing Antibodies ◽  
Viral Vector ◽  
Young Patients ◽  
Clotting Factors ◽  
Liver Transaminase ◽  
Long Term Follow Up ◽  
Recent Phase ◽  
Universal Applicability

Recent phase I/II adeno-associated viral vector-mediated gene therapy clinical trials have reported remarkable success in ameliorating disease phenotype in hemophilia A and B. These trials, which highlight the challenges overcome through decades of preclinical and first in human clinical studies, have generated considerable excitement for patients and caregivers alike. Optimization of vector and transgene expression has significantly improved the ability to achieve therapeutic factor levels in these subjects. Long-term follow-up studies will guide standardization of the approach with respect to the combination of serotype, promoter, dose, and manufacturing processes and inform safety for inclusion of young patients. Certain limitations preclude universal applicability of gene therapy, including transient liver transaminase elevations due to the immune responses to vector capsids or as yet undefined mechanisms, underlying liver disease from iatrogenic viral hepatitis, and neutralizing antibodies to clotting factors. Integrating vectors show promising preclinical results, but manufacturing and safety concerns still remain. The prospect of gene editing for correction of the underlying mutation is on the horizon with considerable potential. Herein, we review the advances and limitations that have resulted in these recent successful clinical trials and outline avenues that will allow for broader applicability of gene therapy.

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