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At least 19 recordsLinked to original sources
PubMedDate not supplied

Judaism, genetic screening and genetic therapy.

Genetic screening, gene therapy and other applications of genetic engineering are permissible in Judaism when used for the treatment, cure, or prevention of disease. Such genetic manipulation is not considered to be a violation of God's natural law, but a legitimate implementation of the biblical mandate to heal. If Tay-Sachs disease, diabetes, hemophilia, cystic fibrosis, Huntington's disease or other genetic diseases can be cured or prevented by "gene surgery," then it is certainly permitted in Jewish law. Genetic premarital screening is encouraged in Judaism for the purpose of discouraging at-risk marriages for a fatal illness such as Tay-Sachs disease. Neonatal screening for treatable conditions such as phenylketonuria is certainly desirable and perhaps required in Jewish law. Preimplantation screening and the implantation of only "healthy" zygotes into the mother's womb to prevent the birth of an affected child are probably sanctioned in Jewish law. Whether or not these assisted reproduction techniques may be used to choose the sex of one's offspring, to prevent the birth of a child with a sex-linked disease such as hemophilia, has not yet been ruled on by modern rabbinic decisions. Prenatal screening with the specific intent of aborting an affected fetus is not allowed according to most rabbinic authorities, although a minority view permits it "for great need." Not to have children if both parents are carriers of genetic diseases such as Tay-Sachs is not a Jewish option. Preimplantation screening is preferable. All screening test results must remain confidential. Judaism does not permit the alteration or manipulation of physical traits and characteristics such as height, eye and hair color, facial features and the like, when such change provides no useful benefit to mankind. On the other hand, it is permissible to clone organisms and microorganisms to facilitate the production of insulin, growth hormone, and other agents intended to benefit mankind and to cure and treat diseases.

Adolescent↗
PubMedDate not supplied

Cellular genetic therapy.

Cellular genetic therapy is the ultimate frontier for those pathologies that are consequent to a specific nonfunctional cellular type. A viable cure for there kinds of diseases is the replacement of sick cells with healthy ones, which can be obtained from the same patient or a different donor. In fact, structures can be corrected and strengthened with the introduction of undifferentiated cells within specific target tissues, where they will specialize into the desired cellular types. Furthermore, consequent to the recent results obtained with the transdifferentiation experiments, a process that allows the in vitro differentiation of embryonic and adult stem cells, it has also became clear that many advantages may be obtained from the use of stem cells to produce drugs, vaccines, and therapeutic molecules. Since stem cells can sustain lineage potentials, the capacity for differentiation, and better tolerance for the introduction of exogenous genes, they are also considered as feasible therapeutic vehicles for gene therapy. In fact, it is strongly believed that the combination of cellular genetic and gene therapy approaches will definitely allow the development of new therapeutic strategies as well as the production of totipotent cell lines to be used as experimental models for the cure of genetic disorders.

Adult↗
PubMedDate not supplied

Ethical issues in genetic therapy.

Ethical issues in genetic therapy involve the use of genetic science for human good and the avoidance of preventable harms. Immediate issues are the control and confidentiality of results of genetic testing, possible discrimination against those found to have genetic diseases, and the just allocation of beneficial genetic therapies. Less practical, but possibly more significant, dilemmas involve the use of genetic science in ways that go beyond prevention and cure of disease. Such use as trait enhancement and "neo-eugenics" raise troubling ethical concerns.

Attitude to Health↗
PubMed2000

Genetic therapy for pain management.

Two approaches to genetic therapy for the management of chronic pain have recently been investigated in animal models of pain. First, transgene-mediated delivery of antinociceptive molecules to the cerebrospinal fluid has been performed with engineered cell lines transplanted to the subarachnoid space and with recombinant adenoviruses that transduce pia mater cells. Second, the phenotype of nociceptive neurons has been altered by recombinant herpes viruses overexpressing antinociceptive peptides or reducing expression of endogenous nociceptive molecules. Both approaches attenuate or reverse persistent nociceptive states, suggesting use in the development of genetic therapy for pain management in humans.

Genetic Therapy↗
PubMed1991

Commentary: how do we think about the ethics of human germ-line genetic therapy?

The line between germ-line genetic therapy and somatic cell is more and more difficult to discern. With new abilities to effect germ-line genetic therapy it is less clear why such therapy should not be undertaken. Nonetheless, questions persist as to who is the patient in such therapy and about the extent of discretion that should be allowed prospective parents and the physician/researcher.

Ethics, Medical↗
PubMed1998

[Genetic therapy for the nervous system: a trend in modern neurology].

INTRODUCTION: Genetic therapy is in itself a new type of treatment, of potential use in many neurological conditions currently considered to be resistant to conventional treatment. Great advances have been made in the construction of vectors of expression and carriers of viral genes, thus work is starting on the characterization of target cells for neuronal genetic therapy. DEVELOPMENT: As a result of advances in this field, two methods of genetic transference have evolved. One, 'in vivo', involves transfection of genetic material by means of chemical or viral agents. The 'ex vivo' variant depends on manipulation of culture cells to subsequently inject them into the host organism with a view to correcting the cell phenotype. Both methods have been used in preliminary experiments designed to test the efficacy of genetic transference for improvement of dysfunction of the nervous system. At the present time there is much experimentation with the use of genetic transference using modified cells to synthetize growth factors or key enzymes of the neurotransmission process in biomodels of Parkinsonism and Alzheimer amongst other conditions. CONCLUSIONS: Genetic therapy, as is shown in this review, has great therapeutic potential for nervous diseases which are very severe and complex. There is certainly a long way to go to perfect these techniques, particularly with regard to biological security and regulation of the element transferred. However, when it is used it will mean a major qualitative change in the treatment of nervous system disorders which are at present a cause of severe handicap and have little chance of treatment.

Animals↗
PubMed1993

Genetic therapy of human neoplastic disease.

Molecular biology has provided clinical investigators and basic scientists with the tools to identify those changes present within neoplastic hematopoietic and epithelial cells that lead to the evolution of unregulated patterns of cell growth. This information has made possible the development of therapy that involves genetic modification of either the normal hematopoietic cells (for chemoprotection), or the tumor cells themselves to suppress the growth of these cells. This article will summarize the clinical and laboratory data that is evolving in this area.

Animals↗
PubMed1997

Progress in transcriptionally targeted and regulatable vectors for genetic therapy.

Safety is an important consideration in the development of genetic therapy protocols; for example, proteins that are therapeutic in the context of one tissue may be harmful in another. This is particularly relevant to suicide gene strategies for cancer, which require in vivo delivery of DNA and which, in general, demand that the therapeutic product be limited as far as possible to malignant cells. This has led to a requirement for "transcriptionally targeted" vectors that can restrict the expression of the therapeutic sequence to appropriate cells. Furthermore, there may be a therapeutic window for certain proteins such that levels of expression below and above certain thresholds may be ineffective or toxic, respectively. Therefore, it would also be desirable to create vectors that allow exogenous control of expression, so that levels of the therapeutic protein can be raised or lowered according to therapeutic need. In the context of transcriptional targeting, one may sometimes use cis-acting sequences to limit transgene expression to the target cell type. In genetic therapy for cancer, for example, it may be possible to identify and use transcriptional control elements that drive expression of proteins unique to, or over-expressed in, malignant cells. These controls would greatly reduce collateral expression of the transgene, and hence reduce toxicity to healthy cells. With regard to exogenous control of expression subsequent to transduction, several synthetic gene regulation systems have now been produced. In these systems, an inducer or repressor acts on a synthetic transcription factor that recognizes motifs unique to the promoter of the transgene; this allows regulated expression of the therapeutic protein without nonspecific effects on cellular promoters. It is likely that a vector will soon be produced in which tissue-restricted expression of the synthetic transcription factor is combined with regulatable transgene expression thereby allowing precise control of therapeutic protein production in specific tissues via administration of an inducing or repressing agent.

Animals↗
PubMed2026

Exploring Genetic Therapies Targeting Amyotrophic Lateral Sclerosis in Animal Models: A Systematic Review and Meta-Analysis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disease, for which there is currently no known cure. ALS primarily affects motor neurons, with rapid deterioration, meaning symptoms develop quickly, from problems with speech and muscle weakness to breathing issues and paralysis. This systematic review aimed to explore the preclinical efficacy of various genetic therapies used to target ALS using in&#xa0;vivo rodent models. METHODS: In vivo studies of genetic therapies targeting ALS and its symptoms published between January 2015 and December 2025 were included in this review. The following databases were used: Web of Science, Scopus and PubMed. The primary outcome investigated was the total number of motor neurons, with secondary outcomes of rodent survival and muscle function by observing rotarod performance also being analysed. The SYRCLE tool was used to assess risk of bias in included studies. RESULTS: Of the 451 studies identified by searching the databases, 53 studies were found to be eligible for this systematic review. The articles were divided into subcategories depending on the gene target of each therapy. Meta-analysis of outcomes within appropriate studies showed significant improvements for the majority of selected outcomes (p&#x2009;<&#x2009;0.05), favouring genetic therapy intervention. CONCLUSIONS: Results suggest that genetic therapies in rodent models targeting ALS are effective. However, due to a high risk of bias in preclinical studies, further high-quality studies are warranted to support this conclusion and onward translation into the clinic.

Animals↗
PubMed1990

A genetic therapy for familial hypercholesterolemia.

The WHHL rabbit serves as an animal model for the human genetic disease, familial hypercholesterolemia. In initial studies aimed at the development of a genetic therapy for familial hypercholesterolemia (i.e., introduction of a normal LDL receptor gene), WHHL rabbit skin fibroblasts were transduced with a retroviral vector expressing a normal human LDL receptor. Correction of the WHHL rabbit genetic defect in vitro was confirmed. Autologous fibroblasts expressing LDL receptors were reimplanted in donor rabbits and were found to survive and express the recombinant receptor in vivo for up to 4 weeks. In vivo LDL receptor expression by autologous cells stably transduced with functioning LDL receptors is possible. Transduction of greater numbers of cells along with increased cell survival in vivo may eventually lead to a specific and effective genetic therapy for familial hypercholesterolemia.

Animals↗
PubMed1997

Genetic therapy, person-regarding reasons and the determination of identity.

It has been argued, for example by Ingmar Persson, that genetic therapy performed on a conceptus does not alter the identity of the person that develops from it, even if we are essentially persons. If this claim is true then there can be person-regarding reasons for performing genetic therapy on a conceptus. Here it is argued that such person-regarding reasons obtain only if we are not essentially persons but essentially animals. This conclusion requires the defeat of the origination theory, which says that personal identity is determined by the identity of the foetus from which one originates. It is argued that the origination theory is false in the special case relevant to performing genetic therapy on a conceptus for person-regarding reasons.

Altruism↗
PubMed1997

Genetic therapy. Past, present, and future.

The early stages of genetic therapy present challenges for clinicians and basic scientists. Clinicians must become familiar with new terminology and concepts, and must keep a perspective on the new field in the face of inflated claims and high-profile failures. Basic scientists must continually return to disease models and to patients to determine what are the proper safety issues and relevant efficacy questions for specific diseases and vector systems. And in an era of instant information, all concerned parties must be careful about how progress is communicated to colleagues, patients, and the lay public.

Forecasting↗
PubMed1995

Genetic therapy, identity and the person-regarding reasons.

It has been argued that there can be no person-regarding reasons for practising genetic therapy, since it affects identity and causes to exist an individual who would not otherwise have existed. And there can be no such reasons for causing somebody to exist because existing cannot be better for an individual than never existing. In the present paper, both of these claims are denied. It is contended, first, that in practically all significant cases genetic therapy will not affect the identity of beings of our kind. This is so irrespective of whether, essentially, we are beings with minds or beings of a certain biological species, the human one. Second, it is contended that, even if genetic therapy were to affect our identity, there could be person-regarding reasons for conducting it, for existence can be better than non-existence for the individual.

Beginning of Human Life↗
PubMed2001

Pharmacologic and genetic therapy for childhood muscular dystrophies.

The outstanding advances in the molecular characterization of muscle diseases, including muscular dystrophies, inflammatory myopathies, and ion channel disorders, have resulted in the identification of potential targets for pharmacologic and genetic therapy in the best characterized of these diseases. The most common myopathy in children, Duchenne muscular dystrophy (DMD), is the focus of active pharmacologic clinical trials. Genetic transfer therapy research for this and other dystrophies is rapidly moving forward. However, as new approaches for treatment are being actively investigated, the current modality of treatment for all myopathies is still in the realm of physical medicine and rehabilitation. The focus of this review is on the advances in pharmacologic and genetic therapy research in DMD and limb girdle muscular dystrophies.

Animals↗
PubMed2005

Genetic therapy in gliomas: historical analysis and future perspectives.

High-grade gliomas are relatively frequent in adults, and consist of the most malignant kind of primary brain tumor. Being resistant to standard treatment modalities such as surgery, radiation, and chemotherapy, it is fatal within 1 to 2 years of onset of symptoms. Although several gene therapy systems proved to be efficient in controlling or eradicating these tumors in animal models, the clinical studies performed so far were not equally successful. Most clinical studies showed that methodologies that increase tumor infection/transduction and, consequently confer more permanent activity against the tumor, will lead to enhanced therapeutic results. Due to the promising practical clinical benefits that can be expected for the near future, an exposition to the practicing neurosurgeon about the basic issues in genetic therapy of gliomas seems convenient. Among the main topics, we shall discuss anti-tumoral mechanisms of various genes that can be transfected, the advantages and drawbacks of the different vectors utilized, the possibilities of tumor targeting by modifications in the native tropism of virus vectors, as well as the different physical methods for vector delivery to the tumors. Along with the exposition we will also review of the history of the genetic therapy for gliomas, with special focus on the main problems found during the advancement of scientific discoveries in this area. A general analysis is also made of the present state of this promising therapeutic modality, with reference to the problems that still must be solved and the new paradigms for future research in this area.

Animals↗
PubMed2002

Combination genetic therapy to inhibit HIV-1.

Compared with single agents, combination antilentiviral pharmacotherapy targets multiple HIV-1 functions simultaneously, maximizing efficacy and decreasing chances of escape mutations. Combination genetic therapy could theoretically enhance efficacy similarly, but delivery of even single genes to high percentages of hematopoietic cells or their derivatives has proven problematic. Because of their high efficiency of gene delivery, we tested recombinant SV40-derived vectors (rSV40s) for this purpose. We made six rSV40s, each carrying a different transgene that targeted a different lentiviral function. We tested the ability of these constructs, individually and in double and triple combinations, to protect SupT1 human T lymphoma cells from HIV-1 challenge. Single chain antibodies (SFv) against CXCR4 and against HIV-1 reverse transcriptase (RT) and integrase (IN) were used, as were polymeric TAR decoys (PolyTAR) and a dominant-negative mutant of HIV-1 Rev (RevM10). Immunostaining showed that virtually all doubly treated cells expressed both transgenes. All transgenes individually protected from HIV-1 but, except for anti-CXCR4 SFv, their effectiveness diminished as challenge doses increased from 40 through 2500 tissue culture infectious dose(50) (TCID(50))/10(6) cells. However, all combinations of transgenes protected target cells better than individual transgenes, even from the highest challenge doses. Thus, combination gene therapies may inhibit HIV-1 better than single agents, and rSV40s may facilitate delivery of multigene therapeutics.

Genetic Therapy↗