Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies.

ABSTRACT: Central Nervous System (CNS) homeostasis and function rely on intercellular synchronization of metabolic pathways. Developmental and neurochemical imbalances arising from mutations are frequently associated with devastating and often intractable neurological dysfunction. In the absence of pharmacological treatment options, but with knowledge of the genetic cause underlying the pathophysiology, gene therapy holds promise for disease control. Consideration of leukodystrophies provide a case in point; we review cell type - specific expression pattern of the disease - causing genes and reflect on genetic and cellular treatment approaches including ex vivo hematopoietic stem cell gene therapies and in vivo approaches using adeno-associated virus (AAV) vectors. We link recent advances in vectorology to glial targeting directed towards gene therapies for specific leukodystrophies and related developmental or neurometabolic disorders affecting the CNS white matter and frame strategies for therapy development in future.

SUBMITTER: von Jonquieres G

PROVIDER: S-EPMC8258421 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Emerging treatments for pediatric leukodystrophies.

Project description:The leukodystrophies are a heterogeneous group of inherited disorders with broad clinical manifestations and variable pathologic mechanisms. Improved diagnostic methods have allowed identification of the underlying cause of these diseases, facilitating identification of their pathologic mechanisms. Clinicians are now able to prioritize treatment strategies and advance research in therapies for specific disorders. Although only a few of these disorders have well-established treatments or therapies, a number are on the verge of clinical trials. As investigators are able to shift care from symptomatic management of disorders to targeted therapeutics, the unmet therapeutic needs could be reduced for these patients.

| S-EPMC5712822 | biostudies-literature

Adenosine Metabolism: Emerging Concepts for Cancer Therapy.

Project description:Adenosine is a key metabolic and immune-checkpoint regulator implicated in the tumor escape from the host immune system. Major gaps in knowledge that impede the development of effective adenosine-based therapeutics include: (1) lack of consideration of redundant pathways controlling ATP and adenosine levels; (2) lack of distinction between receptor-dependent and -independent effects of adenosine, and (3) focus on extracellular adenosine without consideration of intracellular metabolism and compartmentalization. In light of current clinical trials, we provide an overview of adenosine metabolism and point out the need for a more careful evaluation of the entire purinome in emerging cancer therapies.

| S-EPMC7224341 | biostudies-literature

Emerging Concepts and Technologies in Vaccine Development.

Project description:Despite the success of vaccination to greatly mitigate or eliminate threat of diseases caused by pathogens, there are still known diseases and emerging pathogens for which the development of successful vaccines against them is inherently difficult. In addition, vaccine development for people with compromised immunity and other pre-existing medical conditions has remained a major challenge. Besides the traditional inactivated or live attenuated, virus-vectored and subunit vaccines, emerging non-viral vaccine technologies, such as viral-like particle and nanoparticle vaccines, DNA/RNA vaccines, and rational vaccine design, offer innovative approaches to address existing challenges of vaccine development. They have also significantly advanced our understanding of vaccine immunology and can guide future vaccine development for many diseases, including rapidly emerging infectious diseases, such as COVID-19, and diseases that have not traditionally been addressed by vaccination, such as cancers and substance abuse. This review provides an integrative discussion of new non-viral vaccine development technologies and their use to address the most fundamental and ongoing challenges of vaccine development.

| S-EPMC7554600 | biostudies-literature

Glial progenitor cell-based treatment of the childhood leukodystrophies.

Project description:The childhood leukodystrophies comprise a group of hereditary disorders characterized by the absence, malformation or destruction of myelin. These disorders share common clinical, radiological and pathological features, despite their diverse molecular and genetic etiologies. Oligodendrocytes and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group of non-lysosomal metabolic leukodystrophies, may all be appropriate candidates for glial progenitor cell-based treatment. Nonetheless, a variety of specific challenges remain before this therapeutic strategy can be applied to children. These include timely diagnosis, before irreparable neuronal injury has ensued; understanding the natural history of the targeted disease; defining the optimal cell phenotype for each disorder; achieving safe and scalable cellular compositions; designing age-appropriate controlled clinical trials; and for autologous therapy of genetic disorders, achieving the safe genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease.

| S-EPMC5340082 | biostudies-literature

Noncoding RNAs in Glioblastoma: Emerging Biological Concepts and Potential Therapeutic Implications.

Project description:Noncoding RNAs (ncRNAs) have emerged as a novel class of genomic regulators, ushering in a new era in molecular biology. With the advent of advanced genetic sequencing technology, several different classes of ncRNAs have been uncovered, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs), which have been linked to many important developmental and disease processes and are being pursued as clinical and therapeutic targets. Molecular phenotyping studies of glioblastoma (GBM), the most common and lethal cancer of the adult brain, revealed that several ncRNAs are frequently dysregulated in its pathogenesis. Additionally, ncRNAs regulate many important aspects of glioma biology including tumour cell proliferation, migration, invasion, apoptosis, angiogenesis, and self-renewal. Here, we present an overview of the biogenesis of the different classes of ncRNAs, discuss their biological roles, as well as their relevance to gliomagenesis. We conclude by discussing potential approaches to therapeutically target the ncRNAs in clinic.

| S-EPMC8037102 | biostudies-literature

Emerging concepts of shear stress in placental development and function.

Project description:Blood flow, and the force it generates, is critical to placental development and function throughout pregnancy. This mechanical stimulation of cells by the friction generated from flow is called shear stress (SS) and is a fundamental determinant of vascular homeostasis, regulating remodelling and vasomotor tone. This review describes how SS is fundamental to the establishment and regulation of the blood flow through the uteroplacental and fetoplacental circulations. Amongst the most recent findings is that alongside the endothelium, embryonic stem cells and the villous trophoblast are mechanically sensitive. A complex balance of forces is required to enable effective establishment of the uteroplacental circulation, while protecting the embryo and placental villi. SS also generates flow-mediated vasodilatation through the release of endothelial nitric oxide, a process vital for adequate placental blood flow. The identification of SS sensors and the mechanisms governing how the force is converted into biochemical signals is a fast-paced area of research, with multiple cellular components under investigation. For example, the Piezo1 ion channel is mechanosensitive in a variety of tissues including the fetoplacental endothelium. Enhanced Piezo1 activity has been demonstrated in response to the Yoda1 agonist molecule, suggesting the possibility for developing tools to manipulate these channels. Whether such agents might progress to novel therapeutics to improve blood flow through the placenta requires further consideration and research.

| S-EPMC6554190 | biostudies-literature

Emerging Immunogenicity and Genotoxicity Considerations of Adeno-Associated Virus Vector Gene Therapy for Hemophilia.

Project description:Adeno-associated viral (AAV) vector gene therapy has shown promise as a possible cure for hemophilia. However, immune responses directed against AAV vectors remain a hurdle to the broader use of this gene transfer platform. Both innate and adaptive immune responses can affect the safety and efficacy of AAV vector-mediated gene transfer in humans. These immune responses may be triggered by the viral capsid, the vector's nucleic acid payload, or other vector contaminants or excipients, or by the transgene product encoded by the vector itself. Various preclinical and clinical strategies have been explored to overcome the issues of AAV vector immunogenicity and transgene-related immune responses. Although results of these strategies are encouraging, more efficient approaches are needed to deliver safe, predictable, and durable outcomes for people with hemophilia. In addition to durability, long-term follow-up of gene therapy trial participants will allow us to address potential safety concerns related to vector integration. Herein, we describe the challenges with current methodologies to deliver optimal outcomes for people with hemophilia who choose to undergo AAV vector gene therapy and the potential opportunities to improve on the results.

| S-EPMC8199697 | biostudies-literature

Hybrid biosynthetic gene therapy vector development and dual engineering capacity.

Project description:Genetic vaccines offer a treatment opportunity based upon successful gene delivery to specific immune cell modulators. Driving the process is the vector chosen for gene cargo packaging and subsequent delivery to antigen-presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this work, we present the development and assessment of a hybrid gene delivery vector containing biological and biomaterial components. Each component was chosen to design and engineer gene delivery separately in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and a biomaterial [poly(beta-amino ester)]-coated outer surface allowed the simultaneous application of molecular biology and polymer chemistry to address barriers associated with APC gene delivery, which include cellular uptake and internalization, phagosomal escape, and intracellular cargo concentration. The approach combined and synergized normally disparate vector properties and tools, resulting in increased in vitro gene delivery beyond individual vector components or commercially available transfection agents. Furthermore, the hybrid device demonstrated a strong, efficient, and safe in vivo humoral immune response compared with traditional forms of antigen delivery. In summary, the flexibility, diversity, and potential of the hybrid design were developed and featured in this work as a platform for multivariate engineering at the vector and cellular scales for new applications in gene delivery immunotherapy.

| S-EPMC4151754 | biostudies-literature

PRION 2019 emerging concepts

Project description: Not available

| S-EPMC6738495 | biostudies-literature

Emerging Concepts and Novel Strategies in Radiation Therapy for Laryngeal Cancer Management.

Project description:Laryngeal squamous cell carcinoma is the second most common head and neck cancer. Its pathogenesis is strongly associated with smoking. The management of this disease is challenging and mandates multidisciplinary care. Currently, accepted treatment modalities include surgery, radiation therapy, and chemotherapy-all focused on improving survival while preserving organ function. Despite changes in smoking patterns resulting in a declining incidence of laryngeal cancer, the overall outcomes for this disease have not improved in the recent past, likely due to changes in treatment patterns and treatment-related toxicities. Here, we review emerging concepts and novel strategies in the use of radiation therapy in the management of laryngeal squamous cell carcinoma that could improve the relationship between tumor control and normal tissue damage (therapeutic ratio).

| S-EPMC7352689 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data