Projects and Grants
Groundwork for Gene Therapy
At least since the nineteenth century, with Gregor Mendel's experiments describing the essential laws of heredity, it has been clear that important features are inherited by a defined and predictable mechanism. The carrier of this information remained, however, unknown. Then, in the 1940s, Oswald Avery and colleagues at Rockefeller University in New York were successful in the identification of the carrier of genetic information, demonstrating that the information is encoded by DNA. Only a decade later, in 1953, Watson and Crick proposed that DNA is a double helix — immediately suggesting how this structure could be used to replicate and inherit the genetic information. This was followed by the ingenious experiments of Nirenberg and Khorana that resulted in the deciphering of the genetic code.
The discovery of restriction enzymes and their use in molecular biology — by Arber, Nathans and Smith — was a watershed moment, changing forever how life sciences are done. This discovery made genetic manipulation possible — first in bacteria now in all species. Indeed in 1981, the first transgenic mice were created. It is remarkable that only 20 years after the discovery of the first restriction enzyme, the first gene therapy experiment was approved by the NIH in 1990 for the treatment of a four-year-old girl with a rare immune system disorder.
Recent Past, Present, and Future
With the recent decoding of the human genome, there is no shortage in targets for gene therapeutic applications. They range from treatment of classical genetic disorders, often of monogeneic origin, such as cystic fibrosis, lysosomal storage diseases, bleeding disorders, sickle cell anemia, and so on, to more complex disorders with genetic components such as diabetes, cardiovascular disorders, and cancer. For some of the major diseases, gene therapy is one possible treatment; for others, it is likely the most promising approach. Despite the fact that gene therapy is a scientifically sound concept, success stories remain scarce.
So far, there is only one reported clinical success, the treatment of children suffering from X-linked SCID (severe combined immuno deficiency). The therapeutic gene in this case was delivered by a retroviral vector. Tragically, it became recently clear that, as a result of an oncogenic insertion of the viral genome, three of the approximately ten treated children acquired a leukemia like disease. One of these children recently died as a result of this complication. This case and the tragic death of Jesse Gelsinger in a clinical trial using adenoviral vectors are forceful illustrations that gene therapy remains a daunting technical challenge fraught with serious dangers.
These cases also illustrate that one of the major limitations in the field of gene therapy remains the absence of an ideal gene delivery vehicle. As a result, there can be little doubt that only substantial progress in vector development will allow gene therapy to fulfill its potential as one of the main new avenues of medical treatment of the twenty-first century.
Note: The images on this page are not in the public domain. The images can only be freely used for educational purposes.
Projects and Grants
Groundwork for Gene Therapy
At least since the nineteenth century, with Gregor Mendel's experiments describing the essential laws of heredity, it has been clear that important features are inherited by a defined and predictable mechanism. The carrier of this information remained, however, unknown. Then, in the 1940s, Oswald Avery and colleagues at Rockefeller University in New York were successful in the identification of the carrier of genetic information, demonstrating that the information is encoded by DNA. Only a decade later, in 1953, Watson and Crick proposed that DNA is a double helix — immediately suggesting how this structure could be used to replicate and inherit the genetic information. This was followed by the ingenious experiments of Nirenberg and Khorana that resulted in the deciphering of the genetic code.
The discovery of restriction enzymes and their use in molecular biology — by Arber, Nathans and Smith — was a watershed moment, changing forever how life sciences are done. This discovery made genetic manipulation possible — first in bacteria now in all species. Indeed in 1981, the first transgenic mice were created. It is remarkable that only 20 years after the discovery of the first restriction enzyme, the first gene therapy experiment was approved by the NIH in 1990 for the treatment of a four-year-old girl with a rare immune system disorder.
Recent Past, Present, and Future
With the recent decoding of the human genome, there is no shortage in targets for gene therapeutic applications. They range from treatment of classical genetic disorders, often of monogeneic origin, such as cystic fibrosis, lysosomal storage diseases, bleeding disorders, sickle cell anemia, and so on, to more complex disorders with genetic components such as diabetes, cardiovascular disorders, and cancer. For some of the major diseases, gene therapy is one possible treatment; for others, it is likely the most promising approach. Despite the fact that gene therapy is a scientifically sound concept, success stories remain scarce.
So far, there is only one reported clinical success, the treatment of children suffering from X-linked SCID (severe combined immuno deficiency). The therapeutic gene in this case was delivered by a retroviral vector. Tragically, it became recently clear that, as a result of an oncogenic insertion of the viral genome, three of the approximately ten treated children acquired a leukemia like disease. One of these children recently died as a result of this complication. This case and the tragic death of Jesse Gelsinger in a clinical trial using adenoviral vectors are forceful illustrations that gene therapy remains a daunting technical challenge fraught with serious dangers.
These cases also illustrate that one of the major limitations in the field of gene therapy remains the absence of an ideal gene delivery vehicle. As a result, there can be little doubt that only substantial progress in vector development will allow gene therapy to fulfill its potential as one of the main new avenues of medical treatment of the twenty-first century.
Note: The images on this page are not in the public domain. The images can only be freely used for educational purposes.
