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Results for “Working Group on Human Gene Therapy”

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At least 19 recordsLinked to original sources
PubMed1994

A review of current basic approaches to gene therapy.

Over the past decade methods for delivering genes into mammalian cells aimed at subsequent expression of the transferred sequences from the host cell have been developed. Potential therapeutic applications have been envisaged and have raised great interest. Though procedures based on gene targeting will not enter clinical protocols prior to the solving of fundamental issues, procedures based on gene addition are currently underway. The expected benefit of genetic modification of somatic cells needs to be carefully assessed and confronted to its potential risks. Whatever the technological strategy, non-propagation and non-transmission of the gene transfer delivery system is mandatory. Preclinical studies covering a large range of pathologies are currently underway; primarily aimed at demonstrating rather the technological feasibility of various approaches than true therapeutic efficacy. Technological improvements and the solving of basic issues dealing with both the regulation of gene expression and the biology of cell transplantation are still required in order for gene therapy to enter a phase of clinical efficacy. Pluri-disciplinarity only will allow for fruitful exchanges between investigators in the basic sciences and therapists. This has been the basis for creating a European Working group on human Gene Transfer and therapy (EWGT). Whatever the interest raised by gene therapy and its innovatory potential, the relevance of this approach should carefully be considered 1st) in terms of economical constraints and ethics; 2nd) in the context of an overall therapeutic strategy, in particular in the case of acquired disease like cancer, and confronted to alternative treatments such as targeted drugs.

Adenoviridae↗
PubMed2000

Group II introns designed to insert into therapeutically relevant DNA target sites in human cells.

Mobile group II intron RNAs insert directly into DNA target sites and are then reverse-transcribed into genomic DNA by the associated intron-encoded protein. Target site recognition involves modifiable base-pairing interactions between the intron RNA and a >14-nucleotide region of the DNA target site, as well as fixed interactions between the protein and flanking regions. Here, we developed a highly efficient Escherichia coli genetic assay to determine detailed target site recognition rules for the Lactococcus lactis group II intron Ll.LtrB and to select introns that insert into desired target sites. Using human immunodeficiency virus-type 1 (HIV-1) proviral DNA and the human CCR5 gene as examples, we show that group II introns can be retargeted to insert efficiently into virtually any target DNA and that the retargeted introns retain activity in human cells. This work provides the practical basis for potential applications of targeted group II introns in genetic engineering, functional genomics, and gene therapy.

Base Pairing↗
PubMed2002

Ethical, social and public awareness issues in gene therapy EuropaBio.

EuropaBio, the European Association for Bio-industries, represents 40 corporate members operating world wide and 14 national associations (totaling up to 700 small- and medium-sized enterprises) involved in research, development, testing, manufacturing, sales, and distribution of biotechnology-derived products and services in the field of health cae, agriculture, food, and the environment. AGE is a group of researchers and university professors involved in high-level professional activities related to bioethics, and particularly interested in ethical issues related to the development and use of modern technology. It is essential that industry actively participates in, and contributes to, the social debate on emerging technologies. Therefore, EuropaBio presents herein its view on gene therapy and its responsible development and use.

Clinical Trials as Topic↗
PubMed1997

Retrovirus-mediated gene transfer corrects DNA repair defect of xeroderma pigmentosum cells of complementation groups A, B and C.

With the aim to devise a long-term gene therapy protocol for skin cancers in individuals affected by the inherited autosomal recessive xeroderma pigmentosum we transferred the human DNA repair XPA, XPB/ERCC3 and XPC cDNAs, by using the recombinant retroviral vector LXSN, into primary and immortalized fibroblasts obtained from two XP-A, one XP-B (associated with Cockayne's syndrome) and two XP-C patients. After transduction, the complete correction of DNA repair deficiency and functional expression of the transgenes were monitored by UV survival, unscheduled DNA synthesis and recovery of RNA synthesis, and Western blots. The results show that the recombinant retroviruses are highly efficient vectors to transfer and stably express the human DNA repair genes in XP cells and correct the defect of DNA repair of group A, B and C. With our previous results with XPD/ERCC2, the present work extends further promising issues for the gene therapy strategy for most patients suffering from this cancer-prone syndrome.

Blotting, Western↗
PubMed2003

[Gene therapy in the Czech Republic].

Gene therapy represents one of the most promising applications of molecular biology and genetic engineering in medicine. At present its introduction meets series of problems which are of technical, methodological and ethical nature. Although the research in the field of gene therapy in the Czech Republic is on a good level, there is little hope that its achievements will be tested in clinical trials in the near future. In the Czech Republic a law enabling the use of preparations based on the newest biotechnologies in human medicine is missing. Similarly, a production unit capable of preparing the new gene-based drugs according to the Good Manufactory Praxis is not available and the State Institute for Control of Drugs has not any working group fully qualified for their control. The paper proposes actions aimed at solving the present unfavourable situation. The fact that the interest of clinicians in gene therapy is rapidly growing, and that there are signs of increasing interest of public in its achievements, gives good prospects for the introduction of gene therapy into medical praxis in this country in the not very distant future.

Biomedical Research↗
PubMed2006

A fast and reliable single-run method for genotyping of the human cytochrome P450 2C8 gene for different ethnic groups.

Patients vary widely in their response to drug therapy according to their genetic background of drug metabolizing enzymes. The cytochrome P450 enzyme CYP2C8 is one of the major metabolizing enzymes involved in drug metabolism and thus a candidate for routine pharmacogenetic screening. The aim of this work was establishing a fast and reliable method to detect the three CYP2C8 genotypes CYP2C8*2, CYP2C8*3, CYP2C8*4, and the wildtype allele. An established real-time polymerase chain reaction (PCR) to detect two CYP2C8 genotypes was extended by introduction of a third hybridization probe. After optimization of running conditions, the new triplex method was evaluated using 200 DNAs of African origin as templates. Standard methods were performed as controls. The new triplex real-time PCR was fast, reliable and reproducible. The obtained results showed no deviation from the results of the established technique. The polymorphism of the CYP2C8 gene among an African population showed the expected distribution (68% wildtype gene, 32% at least one CYP2C8*2 allele). Pharmacogenetics gain increasing interest in routine medical care to prevent severe adverse effects or the application of ineffective drugs. We here provide a fast, reliable and reproducible method in one single assay run to detect three relevant CYP2C8 alleles independent of the patient's ethnic origin.

Aryl Hydrocarbon Hydroxylases↗
PubMed2005

Therapeutic group programme for women with postnatal depression in rural Victoria: a pilot study.

OBJECTIVE: The aim of this study was to examine the effectiveness of a therapeutic group programme, provided by community health workers, in reducing anxiety and depressive symptoms associated with postnatal depression (PND) among women living in a rural setting. METHOD: A prospective repeated measures design was used. Women reporting difficulties in the postnatal period were recruited through community health services. Training was provided to community health workers, who then facilitated a 9 week group programme (cognitive-behavioural strategies) for women with PND. The Edinburgh Postnatal Depression Scale and the Hospital Anxiety and Depression Scale measured depressive and anxiety symptoms before starting the group programme, at the completion of the programme and at two follow-up times. RESULTS: Fourteen women completed the group programme at two sites in rural Victoria. Comparison of mean anxiety and depressive symptom scores revealed a significant reduction in scores from pre- to post-programme. For those women who also completed the follow-up symptom measurement, this reduction in symptoms was maintained. CONCLUSIONS: The results show that therapeutic group work is an effective intervention that can be applied by community health workers in a rural setting. Challenges for clinicians working with women experiencing PND in rural areas and implications for future research are discussed.

Adult↗
PubMed2004

Amniotic fluid and placental stem cells.

The amniotic fluid and the placenta are unique sources of different populations of stem cells--mesenchymal, hematopoietic, trophoblastic--and, possibly, of more primitive stem cells. Although much of the amniotic cavity/fluid and the placenta share a common embryonic origin, the specific origins of the stem cells found in these two compartments remain to be determined. Accordingly, it is not yet known whether all or part of these two stem-cell subsets are actually the same. The multilineage potential of the different stem cell populations from these two sources has begun to be described but still much remains to be learned. Thus, it is not surprising that clinical applications related to the use of these cells have yet to be reported. Nevertheless, fertile experimental work from many different groups has introduced a number of promising novel therapeutic concepts utilizing these cells, such as in tissue engineering, cell transplantation, and gene therapy.

Amnion↗
PubMed2002

Macrophage-specific gene expression: current paradigms and future challenges.

Cells of the mononuclear phagocyte lineage include macrophages, microglia, osteoclasts, and myeloid dendritic cells. These cell types are all derived from blood monocytes, which are the product of hematopoietic stem cell differentiation. In this review we use specific examples of macrophage-expressed genes to illustrate potential regulatory strategies for directing macrophage-specific gene expression. The examples we have chosen-the human c-fes gene, the murine spi-1 (PU.1) gene, the human RANTES promoter, and the human CD68 gene-illustrate different aspects of constitutive and inducible gene expression in macrophages. One important challenge for future work in this field will be to identify the molecular events that dictate lineage decisions during the differentiation of mononuclear phagocytes from hematopoietic progenitor cells. Another important goal will be to understand how groups of macrophage genes are coordinately expressed in response to physiological, immunological, and inflammatory stimuli. A better understanding of macrophage gene expression may find application in gene therapy, genetic vaccination, and the development of new antiinflammatory drugs.

Animals↗