Gene Therapy

Since the early 1900s, beginning with the astute observation by Sir Archibald Garrod that Mendel’s rules of inheritance in peas could be applied to humans, clinicians and scientists have gradually elucidated the underlying genetic and molecular etiologies of human disease. One century later, the human genome was fully sequenced through the Human Genome Project and has been largely protected as a publicly accessible, nonpatented resource due to the foresight of the project’s leader, Dr Francis Collins. This breakthrough has led to an explosion of research and discovery in genetics and molecular-based therapy.

Genes in the simplest sense provide the instructions for how our bodies work. Although the concept of the gene is ever-evolving, the classical definition of a gene is a sequence of DNA that is transcribed into a messenger RNA and then translated into a protein with a specific purpose or function. There are an estimated 20,000 protein-coding genes, and we know that even a single base pair or letter change in one of these genes can have health consequences, as in sickle cell anemia. Genetics is a complex and evolving field, with new discoveries being made about the importance of noncoding regions, functional RNA, epigenetic regulation of expression beyond the simple DNA code, and redundancy in the code, as is seen with different forms of β-globin. We also know that discovery of conditions and institution of therapies to ameliorate those conditions have changed the natural history, again as may be seen with antibiotic therapy, transfusions, transplant, and stroke prevention in sickle cell disease. So often, patients or parents ask, “Well, if you know the problem with the gene, can’t you just fix the gene?”

Indeed, the idea of gene therapy has intrigued clinicians and scientists for decades. Gene therapy involves one of the following mechanisms: 1) direct editing …