Germline Gene Therapy Research Articles

Molecular genetics and potential gene therapy

Contemporary molecular techniques including gene cloning, DNA sequencing, and gene transfer permit precise and comprehensive analysis of genetic disorders. For example, the molecular basis of hemoglobin synthesis disorders (the thalassemias) can now be ascribed to more than 30 different specific mutations. These affect virtually all aspects of gene expression. The more recent capacity to reintroduce cloned genes into mammalian cells in a functional form has raised the prospect of gene therapy, that is, the replacement of an abnormal gene with its normal counterpart or merely the introduction of a normal gene into a cell containing a defective copy. Genetic correction of enzyme-deficiency disorders whose effects are manifest in bone-marrow-derived cells seems most likely to be amenable to “somatic” (as opposed to germ line) gene therapy. Treatment of severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency may be a suitable model for this approach. This report will review the molecular genetics of ADA, the methods by which ADA gene sequences may be transferred into various cells, and goals for current and future research.

Controlling the bugs. The first decade in the regulation of biotechnology.

In late 1984, the Reagan administration proposed a Coordinated Framework for Regulation of Biotechnology. Its proposed regulatory approach appears less constraining than the deep concerns of the 1970s concerning the risk of biotechnology would have suggested. Several distinctive characteristics of the early period of biotechnology, particularly the role of the research community in developing the initial regulatory system and the extent of federal funding, explain this development. The administration's proposal may attract substantial support. However, implementation may lead to conflicts and problems, especially concerning human germ-line gene therapy and environmental release of viable genetically engineered organisms.

Human gene therapy: scientific and ethical considerations.

The term 'gene therapy' encompasses at least four types of application of genetic engineering for the insertion of genes into humans. The scientific requirements and the ethical issues associated with each type are discussed. Somatic cell gene therapy is technically the simplest and ethically the least controversial. The first clinical trials will probably be undertaken within the next year. Germ line gene therapy will require major advances in our present knowledge and it raises ethical issues that are now being debated. In order to provide guidelines for determining when germ line gene therapy would be ethical, the author presents three criteria which should be satisfied prior to the time that a clinical protocol is attempted in humans. Enhancement genetic engineering presents significant, and troubling, ethical concerns. Except where this type of therapy can be justified on the grounds of preventive medicine, enhancement engineering should not be performed. The fourth type, eugenic genetic engineering, is impossible at present and will probably remain so for the foreseeable future, despite the widespread media attention it has received.