Prospects for Somatic Gene Therapy in the Management of Inborn Errors of Metabolism

1990 ◽  
pp. 671-680
Author(s):  
F. D. Ledley
Keyword(s):  
Gene Therapy ◽  
Inborn Errors Of Metabolism ◽  
Somatic Gene Therapy ◽  
Inborn Errors ◽  
Somatic Gene

Development of High-Capacity Adenoviral Vectors for Gene Therapy

1999 ◽  
Vol 82 (08) ◽  
pp. 547-551 ◽  
Author(s):  
Stefan Kochanek
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Inborn Errors Of Metabolism ◽  
Genetic Disorders ◽  
Vector System ◽  
Somatic Gene Therapy ◽  
Inborn Errors ◽  
Somatic Gene ◽  
The Future ◽  
The Many

IntroductionArticles about mutations that cause genetic disorders frequently include a suggestion that gene therapy will likely provide a cure for the disease in the future. In fact, ongoing efforts to sequence the human genome, to understand the roles of genes during development, and to determine the molecular pathogenesis of disease will almost “naturally” lead to the use of nucleic acids for the treatment of diseases in the future.Somatic gene therapy can be defined as the treatment of inherited or acquired diseases by the introduction and expression of genetic information in somatic cells. Genetic disorders that are caused by loss-of-function mutations might be treated by introducing a functional copy of the mutated gene into the appropriate tissue. Good candidate disorders for somatic gene therapy include the many inborn errors of metabolism, such as hemophilia A or B, which are caused by either a low amount or the complete absence of a single functional gene product. These disorders have been characterized at the DNA level, and the disease-causing mutations can be relatively easily identified in individual patients.Many acquired diseases, such as different types of cancer, are less well-defined at the molecular level. However, because of their frequency and their impact on public health, interest in the development of gene therapy for these disorders is particularly high. In fact, most of the clinical gene therapy trials that have been conducted so far relate to the treatment of malignant tumors. Despite the many ongoing clinical trials, as yet, there have been no clear examples of the successful treatment of any human disease by gene transfer.Possibly the single most important reason preventing a broad application of gene transfer in the treatment of diseases, whether inherited or acquired, is the lack of both safe and effective gene transfer technologies. What are the requirements for the use of a vector as a vehicle for gene transfer in patients with inborn errors of metabolism? The vector should efficiently transport and deliver foreign genes to different cell types, both in vitro and in vivo. Following gene transfer, these genes should be permanently expressed at physiological levels. In many cases, expression will need to be tissue-specific and regulated. The vector should be safe, stable, and easily manufactured to high yields.While several nonviral and viral gene transfer vectors have been tested in different systems, currently, there is no vector system available that meets all of these requirements. With the realization that efficient delivery of genes into tissues is at the heart of successful somatic gene therapy, many research groups are concentrating their efforts on refining the different aspects of the multi-step process of gene transfer.

Somatic Gene Therapy

1991 ◽  
Vol 5 (3) ◽  
pp. 423-432 ◽  
Author(s):  
Charles Hesdorffer ◽  
Dina Markowitz ◽  
Maureen Ward ◽  
Arthur Bank
Keyword(s):  
Gene Therapy ◽  
Somatic Gene Therapy ◽  
Somatic Gene

Correction of the Growth Defect in Dwarf Mice with Nonautologous Microencapsulated Myoblasts—An Alternate Approach to Somatic Gene Therapy

1995 ◽  
Vol 6 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Ayman Al-Hendy ◽  
Gonzalo Hortelano ◽  
Gloria S. Tannenbaum ◽  
Patricia L. Chang
Keyword(s):  
Gene Therapy ◽  
Growth Defect ◽  
Somatic Gene Therapy ◽  
Somatic Gene ◽  
Dwarf Mice

Somatic gene therapy for phenylketonuria and other hepatic deficiencies

1996 ◽  
Vol 19 (4) ◽  
pp. 412-423 ◽  
Author(s):  
R. C. Eisensmith ◽  
S. L. C. Woo
Keyword(s):  
Gene Therapy ◽  
Somatic Gene Therapy ◽  
Somatic Gene

Somatic gene therapy of cancer

1995 ◽  
Vol 121 (S1) ◽  
pp. S37-S37
Author(s):  
M. L. Birnstiel ◽  
T. Schweighoffer ◽  
W. Schmidt ◽  
K. Zatloukal ◽  
G. Maass
Keyword(s):  
Gene Therapy ◽  
Somatic Gene Therapy ◽  
Somatic Gene

Treatment of Inherited Neurometabolic Diseases: The Future

1992 ◽  
Vol 7 (1_suppl) ◽  
pp. S132-S140 ◽  
Author(s):  
Pinar T. Ozand ◽  
Generoso G. Gascon
Keyword(s):  
Gene Therapy ◽  
Bone Marrow ◽  
Autologous Bone Marrow ◽  
Marrow Transplant ◽  
Somatic Gene Therapy ◽  
Autologous Bone Marrow Transplant ◽  
Somatic Gene ◽  
Dividing Cells ◽  
Normal Gene ◽  
Religious Considerations

The past 10 years' experience with bone marrow transplantation from normal, immunologically compatible donors indicates its possible use in various neurometabolic diseases, particularly in a patient who has not suffered irreparable brain damage. This experience may be a prelude to treatment by somatic gene therapy. This can be applied as an autologous bone marrow transplant, grafting the patient's own stem cells inserted with the normal gene. Although somatic gene therapy will be relatively easy for tissues with dividing cells, its application to target tissues with little or no cell division may pose difficulties. Meanwhile, techniques for the preservation, culture, and grafting of fetal neurons in humans have been developed and have been used in the treatment of Parkinson's disease. These procedures could readily be transferred to the treatment of other neurodegenerative diseases that cause significant morbidity, but ethical, legal, and religious considerations must be taken into account. All these efforts promise novel and improved management of inborn neurometabolic errors. (J Child Neurol 1992;7(Suppl):S132-S140.)

The Challenge of Follow-Up for Clinical Trials of Somatic Gene Therapy

1992 ◽  
Vol 3 (6) ◽  
pp. 657-663 ◽  
Author(s):  
Fred D. Ledley ◽  
Baruch Brody ◽  
Claudia A. Kozinetz ◽  
Susan G. Mize
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Somatic Gene Therapy ◽  
Somatic Gene
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