Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Autologous Stem-Cell-Based Gene Therapy for Inherited Disorders: State of the Art and Perspectives.

ABSTRACT: Gene therapy using patient's own stem cells is rapidly becoming an alternative to allogeneic stem cell transplantation, especially when suitably compatible donors cannot be found. The advent of efficient virus-based methods for delivering therapeutic genes has enabled the development of genetic medicines for inherited disorders of the immune system, hemoglobinopathies, and a number of devastating metabolic diseases. Here, we briefly review the state of the art in the field, including gene editing approaches. A growing number of pediatric diseases can be successfully cured by hematopoietic stem-cell-based gene therapy.

SUBMITTER: Staal FJT

PROVIDER: S-EPMC6834641 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Autologous Stem-Cell-Based Gene Therapy for Inherited Disorders: State of the Art and Perspectives.

Staal Frank J T FJT Aiuti Alessandro A Cavazzana Marina M

Frontiers in pediatrics 20191031

Gene therapy using patient's own stem cells is rapidly becoming an alternative to allogeneic stem cell transplantation, especially when suitably compatible donors cannot be found. The advent of efficient virus-based methods for delivering therapeutic genes has enabled the development of genetic medicines for inherited disorders of the immune system, hemoglobinopathies, and a number of devastating metabolic diseases. Here, we briefly review the state of the art in the field, including gene editin ...[more]

PMID: 31737588

Similar Datasets

Lentiviral hematopoietic stem cell gene therapy in inherited metabolic disorders.

Project description:After more than 20 years of development, lentiviral hematopoietic stem cell gene therapy has entered the stage of initial clinical implementation for immune deficiencies and storage disorders. This brief review summarizes the development and applications, focusing on the lysosomal enzyme deficiencies, especially Pompe disease.

| S-EPMC4179920 | biostudies-literature

Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art.

Project description:Background: Gene therapy cannot be yet considered a far perspective, but a tangible therapeutic option in the field of retinal diseases. Although still confined in experimental settings, the preliminary results are promising and provide an overall scenario suggesting that we are not so far from the application of gene therapy in clinical settings. The main aim of this review is to provide a complete and updated overview of the current state of the art and of the future perspectives of gene therapy applied on retinal diseases. Methods: We carefully revised the entire literature to report all the relevant findings related to the experimental procedures and the future scenarios of gene therapy applied in retinal diseases. A clinical background and a detailed description of the genetic features of each retinal disease included are also reported. Results: The current literature strongly support the hope of gene therapy options developed for retinal diseases. Although being considered in advanced stages of investigation for some retinal diseases, such as choroideremia (CHM), retinitis pigmentosa (RP), and Leber's congenital amaurosis (LCA), gene therapy is still quite far from a tangible application in clinical practice for other retinal diseases. Conclusions: Gene therapy is an extremely promising therapeutic tool for retinal diseases. The experimental data reported in this review offer a strong hope that gene therapy will be effectively available in clinical practice in the next years.

| S-EPMC8553993 | biostudies-literature

Brain Stimulation in Eating Disorders: State of the Art and Future Perspectives.

Project description:The management of eating disorders (EDs) is still difficult and few treatments are effective. Recently, several studies have described the important contribution of non-invasive brain stimulation (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and electroconvulsive therapy) and invasive brain stimulation (deep brain stimulation and vagal nerve stimulation) for ED management. This review summarizes the available evidence supporting the use of brain stimulation in ED. All published studies on brain stimulation in ED as well as ongoing trials registered at clinicaltrials.gov were examined. Articles on neuromodulation research and perspective articles were also included. This analysis indicates that brain stimulation in EDs is still in its infancy. Literature data consist mainly of case reports, cases series, open studies, and only a few randomized controlled trials. Consequently, the evidence supporting the use of brain stimulation in EDs remains weak. Finally, this review discusses future directions in this research domain (e.g., sites of modulation, how to enhance neuromodulation efficacy, personalized protocols).

| S-EPMC7465000 | biostudies-literature

Transcriptional profiling of microglia; current state of the art and future perspectives

Project description:Microglia are the tissue macrophages of the central nervous system (CNS) and the first to respond to CNS dysfunction and disease. Gene expression profiling of microglia during development, under homeostatic conditions and in the diseased CNS provided insight in microglia functions and changes thereof. Single cell sequencing studies further contributed to our understanding of microglia heterogeneity in relation to age, sex and CNS disease. Recently, single nucleus gene expression profiling was performed on (frozen) CNS tissue. Transcriptomic profiling of CNS tissues by (single) nucleus RNA-sequencing has the advantage that it can be applied to archived and well stratified frozen specimens. Here, we give an overview of the significant advances recently made in microglia transcriptional profiling. In addition, we present matched cellular and nuclear microglia RNA-seq datasets we generated from mouse and human CNS tissue to compare cellular versus nuclear transcriptomes from fresh and frozen samples. We demonstrate that microglia can be similarly profiled with cell and nucleus profiling, and importantly also with nuclei isolated from frozen tissue. Nuclear microglia transcriptomes are a reliable proxy for cellular transcriptomes. Interestingly, lipopolysaccharide- (LPS)-induced changes in gene expression were even more pronounced in the nuclear transcriptome. In addition, heterogeneity in microglia observed in fresh samples is similarly detected in frozen nuclei of the same donor. Together, these results show that microglia nuclear RNAs obtained from frozen CNS tissue are a reliable proxy for microglia gene expression and cellular heterogeneity and may prove an effective strategy to study of the role of microglia in neuropathology.

2019-08-10 | GSE135618 | GEO

Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art.

Project description:Progressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

| S-EPMC7943682 | biostudies-literature

Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art.

Project description:The need for long-lasting and transformative therapies for mucopolysaccharidoses (MPS) cannot be understated. Currently, many forms of MPS lack a specific treatment and in other cases available therapies, such as enzyme replacement therapy (ERT), do not reach important areas such as the central nervous system (CNS). The advent of newborn screening procedures represents a major step forward in early identification and treatment of individuals with MPS. However, the treatment of brain disease in neuronopathic MPS has been a major challenge to date, mainly because the blood brain barrier (BBB) prevents penetration of the brain by large molecules, including enzymes. Over the last years several novel experimental therapies for neuronopathic MPS have been investigated. Gene therapy and gene editing constitute potentially curative treatments. However, despite recent progress in the field, several considerations should be taken into account. This review focuses on the state of the art of in vivo and ex vivo gene therapy-based approaches targeting the CNS in neuronopathic MPS, discusses clinical trials conducted to date, and provides a vision for the future implications of these therapies for the medical community. Recent advances in the field, as well as limitations relating to efficacy, potential toxicity, and immunogenicity, are also discussed.

| S-EPMC8430935 | biostudies-literature

State-of-the-art 2003 on PKU gene therapy.

Project description:Phenylketonuria (or PKU) is a well-known and widespread genetic disease for which many countries perform newborn screening, and life-long dietary restriction is still the ultimate and effective therapy. However, the diet is complicated, unpalatable, and expensive. The long-term effects of diet discontinuation in adults, except for the serious adverse effects of maternal hyperphenylalaninemia upon the developing fetus, have not been systematically studied, but cognitive decline and neurologic abnormalities have been anecdotally reported. Thus, alternative approaches for PKU therapy, including gene therapy, must be further explored. Here we summarize past present nonviral and viral gene transfer approaches, both in vitro studies and preclinical animal trials, to delivering the PAH gene into liver or other organs as potential alternatives to life-long phenylalanine-restricted dietary therapy.

| S-EPMC2706831 | biostudies-literature

Carbon-based sustainable nanomaterials for water treatment: State-of-art and future perspectives.

Project description:The supply of safe drinking and clean water is becoming increasingly challenging proposition throughout the world. The deployment of environmentally sustainable nanomaterials with unique advantages namely high efficiency and selectivity, earth-abundance, recyclability, low-cost of production processes, and stability, has been a priority although several important challenges and constraints still remained unresolved. Carbon nanomaterials namely activated carbon, multi-walled- and single-walled carbon nanotubes, have been developed and applied as adsorbents for wastewater treatment and purification; graphene and graphene oxide-based nanomaterials as well as carbon and graphene quantum dots-derived nanomaterials have shown significant promise for water and wastewater treatment and purification, especially, for industrial- and pharmaceutical-laden wastes. This review encompasses advanced carbonaceous nanomaterials and methodologies that are deployed for the elimination of contaminants and ionic metals in aqueous media, and as novel nanosorbents for wastewater, drinking and ground water treatment. Additionally, recent trends and challenges pertaining to the sustainable carbon and graphene quantum dots-derived nanomaterials and their appliances for treating and purifying wastewater are highlighted.

| S-EPMC7880008 | biostudies-literature

State-of-the-Art 2019 on Gene Therapy for Phenylketonuria.

Project description:Phenylketonuria (PKU) is considered to be a paradigm for a monogenic metabolic disorder but was never thought to be a primary application for human gene therapy due to established alternative treatment. However, somewhat unanticipated improvement in neuropsychiatric outcome upon long-term treatment of adults with PKU with enzyme substitution therapy might slowly change this assumption. In parallel, PKU was for a long time considered to be an excellent test system for experimental gene therapy of a Mendelian autosomal recessive defect of the liver due to an outstanding mouse model and the easy to analyze and well-defined therapeutic end point, that is, blood l-phenylalanine concentration. Lifelong treatment by targeting the mouse liver (or skeletal muscle) was achieved using different approaches, including (1) recombinant adeno-associated viral (rAAV) or nonviral naked DNA vector-based gene addition, (2) genome editing using base editors delivered by rAAV vectors, and (3) by delivering rAAVs for promoter-less insertion of the PAH-cDNA into the Pah locus. In this article we summarize the gene therapeutic attempts of correcting a mouse model for PKU and discuss the future implications for human gene therapy.

| S-EPMC6763965 | biostudies-literature

State-of-the-art human gene therapy: part II. Gene therapy strategies and clinical applications.

Project description:In Part I of this Review (Wang and Gao, 2014), we introduced recent advances in gene delivery technologies and explained how they have powered some of the current human gene therapy applications. In Part II, we expand the discussion on gene therapy applications, focusing on some of the most exciting clinical uses. To help readers to grasp the essence and to better organize the diverse applications, we categorize them under four gene therapy strategies: (1) gene replacement therapy for monogenic diseases, (2) gene addition for complex disorders and infectious diseases, (3) gene expression alteration targeting RNA, and (4) gene editing to introduce targeted changes in host genome. Human gene therapy started with the simple idea that replacing a faulty gene with a functional copy can cure a disease. It has been a long and bumpy road to finally translate this seemingly straightforward concept into reality. As many disease mechanisms unraveled, gene therapists have employed a gene addition strategy backed by a deep knowledge of what goes wrong in diseases and how to harness host cellular machinery to battle against diseases. Breakthroughs in other biotechnologies, such as RNA interference and genome editing by chimeric nucleases, have the potential to be integrated into gene therapy. Although clinical trials utilizing these new technologies are currently sparse, these innovations are expected to greatly broaden the scope of gene therapy in the near future.

| S-EPMC4440458 | 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