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Results for “Recombinant DNA Advisory Committee”

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PubMed1996

Gene therapy: basic concepts and recent advances.

After years of preliminary in vitro and in vivo modeling, the first human gene therapy clinical trial was initiated approximately 5 years ago. The experience gained from this trial, and the others that have come after it, has shown that effective and efficient human gene therapy remains a tantalizing but elusive goal. Nevertheless, interest in this area of therapeutics continues to grow and over 100 gene therapy protocols have now been submitted to the Recombinant DNA Advisory Committee ("RAC") of the National Institutes of Health for approval. The goal of these protocols vary, but include correction of inherited gene defects, engineering new traits into cells such as diminished chemosensitivity in the case of bone marrow cells, or, in the case of tumor cells, expression of new immunophenotypes. Marking cells with a gene whose function can easily be detected, thereby rendering the cell traceable in vitro and in vivo is also the goal of several clinical trials. At the same time, different means of gene transfer are been investigated for the efficiency with which they deliver "therapeutic nucleotides" into their cellular targets. In this review, we recount some of the major developments that have occurred in these various areas and discuss their impact on progress in the field.

Animals↗

PubMed1995

Progress toward the treatment of arthritis by gene therapy.

Gene therapy offers several novel advantages to the treatment of arthritis and other joint diseases. Therapeutic genes may be delivered locally to diseased joints or systemically to extra-articular locations using viral or non-viral vectors by ex vivo or in vivo strategies. Pre-clinical experiments with rabbits have demonstrated the utility of using a retrovirus to deliver the human interleukin-1 receptor antagonist to the synovial lining of joints. A human trial based on this principle has been approved by the Recombinant DNA Advisory Committee of NIH and should begin this year.

Animals↗

PubMed1998

[Gene therapy--hopes and fears].

Gene therapy assumes the correction of a genetic defect by the delivery of a correct DNA sequence to the target cells. Depending on the target cells two types gene therapy have been defined: somatic and germinal. By July 1998, 351 protocols of somatic therapy were approved by the Recombinant DNA Advisory Committee. The majority of protocols focus on cancer therapy and monogenic diseases. By now, still there is more unfulfilled expectation than clinically sound achievements, since no effective prevention or successful treatment for genetic diseases or cancer have been developed. Germline genetic modification is considered as the treatment of choice for such a diseases like retinoblastoma. Tay-Sachs, Lesch-Nyhan and metachromatic leuko-dystrophy. This approach which is still illegal or prohibited by rules in many European countries, is gathering more and more advocates. Once we learn how to control gene expression the perspectives for clinical application of gene therapy might be enormous. The safety of genetic modification of gametes or embryonal stem cells remains to be properly addressed and successfully solved. The ethical issues of germinal gene therapy are still the subject of controversial opinions among the scientists, lawyers and philosophers.

Clinical Protocols↗

PubMed2000

Gene therapy for prostate cancer: where are we now?

PURPOSE: The ability to recombine specifically and alter DNA sequences followed by techniques to transfer these sequences or even whole genes into normal and diseased cells has revolutionized medical research and ushered the clinicians of today into the age of gene therapy. We provide urologists a review of relevant background information, outline current treatment strategies and clinical trials, and delineate current challenges facing the field of gene therapy for advanced prostate cancer. MATERIALS AND METHODS: We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from national meetings, relevant to gene therapy and advanced prostate cancer. We selected for review literature representative of the principal scientific background for current gene therapy strategies and National Institutes of Health Recombinant DNA Advisory Committee approved clinical trials. RESULTS: Current prostate cancer gene therapy strategies include correcting aberrant gene expression, exploiting programmed cell death pathways, targeting critical cell biological functions, introducing toxic or cell lytic suicide genes, enhancing the immune system antitumor response and combining treatment with conventional cytotoxic chemotherapy or radiation therapy. CONCLUSIONS: Many challenges lie ahead for gene therapy, including improving DNA transfer efficiency to cells locally and at distant sites, enhancing levels of gene expression and overcoming immune responses that limit the time that genes are expressed. Nevertheless, despite these current challenges it is almost certain that gene therapy will be part of the urological armamentarium against prostate cancer in this century.

Adenoviridae↗

PubMed2001

Gene therapy: progress and challenges.

Gene therapy is the delivery of new genetic material into a patient's somatic cells for the treatment of disease and is made possible through the development of viral and non-viral gene transfer vectors. In the first five years of gene therapy, clinical studies failed to yield efficacy data with the vectors available at that time. The lack of consistent clinical benefit prompted the United States National Institute of Health Recombinant DNA Advisory Committee to evaluate gene therapy research and conclude that substantial improvements in gene transfer vectors were needed in the areas of vector safety and control of the level and duration of gene expression, and to increase the understanding of the biological interaction of gene transfer vectors with the host. We will describe the progress in development of gene delivery technology, focusing on improvements in vector safety, analysis of vector biodistribution and GMP manufacturing of viral and non-viral gene transfer systems over the last six years since the report. Whereas 5 years ago, investigators tested every vector for every potential disease indication, the accumulated database now enables investigators to select a single vector based upon it's known performance in a wide number of animal models and human clinical studies. We will also highlight several directions investigators have taken to improve the safety and efficacy of gene therapy vectors.

Adenoviridae↗

PubMed1990

[First somatic human gene therapy in the USA approved].

The clinical protocol to treat infants with severe combined immuno deficiency due to adenosine deaminase (ADA) deficiency by means of gene thereapy has been approved recently. The Human Gene Therapy Subcommittee and the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH) concluded the review on July 30th and opened the door for the first federally approved somatic Human Gene Therapy.

Adenosine Deaminase↗

PubMed1995

Adeno-associated virus vectors for gene therapy.

Adeno-associated virus type 2 (AAV) is a non-pathogenic DNA virus which has been utilized as a eukaryotic gene transfer vector in vitro and in vivo. AAV possesses a unique set of characteristics which may make it useful for human gene therapy. AAV infection does not require host cell proliferation, although expression from AAV vectors may exhibit a relative preference for actively dividing cells. Both wild-type AAV and AAV vectors tend to persist in infected cells for prolonged periods of time, without any significant adverse consequences for the host. Wild-type AAV integrates frequently in one specific region of chromosome 19, whereas rep-deleted AAV vectors integrate in a less specific fashion in the host cell genome and may also persist in an episomal state. AAV vectors have been used to transduce a wide range of cell types in vitro including respiratory epithelial cells as well as bone marrow and lymphocyte-derived cells. As a prelude to AAV-based gene therapy for cystic fibrosis (CF), in vivo transduction and expression in the lungs has been observed in rodents and non-human primates after direct delivery to the airway surface, without any detectable toxicity. Based on these findings, the National Institutes of Health Recombinant DNA Advisory Committee (RAC) has recently approved a phase I human trial of CF gene therapy using an AAV vector.

Animals↗

PubMed1993

[Present status and future prospects of human gene therapy].

Gene therapy is defined as the treatment of diseases by the transfer of genes into cells. This concept originally emerged as the definitive therapy for genetic disease. However, acquired diseases such as cancer and AIDS are now being considered as its potential targets. The first clinical trial of human gene therapy was in 1990 at the NIH in a 4 year old girl with fatal severe combined immunodeficiency caused by adenosine deaminase deficiency. Blood transfusion with genetically corrected lymphocytes resulted in significant improvement of the function of her immune system. The patient was discharged from hospital and is attending a public school. Immunotherapy for cancer using tumor cells transduced with genes for various cytokines and major histocompatibility antigens (tumor vaccine) has also been initiated at many research hospitals. In addition, gene therapy protocols targeting familial hypercholesterolemia, hemophilia B, cystic fibrosis are underway. Currently, more than 50 clinical protocols have been approved by the Recombinant DNA Advisory Committee at the NIH, and more than 100 patients have already been treated by this innovative therapeutic strategy.

Child, Preschool↗

PubMed1984