Gene therapy offers a new treatment paradigm for curing human disease.
Rather than altering the disease phenotype by using agents who interact
with gene products, or are themselves gene products, gene therapy can
theoretically modify specific genes resulting in disease cure following
a single administration. Initially gene therapy was envisioned for the
treatment of genetic disorders, but is currently being studied in a
wide range of diseases, including cancer, peripheral vascular disease,
arthritis, neurodegenerative disorders and other acquired diseases.
Even though the range of gene therapy strategies is quite diverse,
certain key elements are required for a successful gene therapy
strategy (i.e. cloning). The most elementary of these is that the
relevant gene must be identified and cloned. Upon completion of the
Human Genome Project, gene availability will be unlimited, but until
then the starting point for any gene therapy strategy remains gene
identification and cloning for relevant genes related to the disease.
Once the gene has been identified and cloned, the next consideration
must be expression. Questions pertaining to the efficiency of gene
transfer and gene expression remain at the forefront of gene therapy
research. Currently many debates in the field of gene therapy revolves
around the transfer of desired genes to appropriate cells, and then
obtaining sufficient levels of expression for disease treatment.
Hopefully, future research on gene transfer and tissue-specific gene
expression will resolve these issues in the majority of gene therapy
protocols. Other important considerations for a gene therapy strategy
include a sufficient understanding of the pathogenesis of the targeted
disorder, potential side effects of the gene therapy treatment, and
understanding of the target cells to receive the gene therapy.
Gene transfer vector is the mechanism by which the gene is transferred
into a cell. Currently there are at least 150 clinical gene therapy
protocols worldwide. Since the approval process for these protocols is
not as public outside the U.S., it is difficult to obtain an exact
number of worldwide protocols. Of the publicized protocols, 125 are
approved in the United States, 48 in Europe and at least 1 each in
China and Japan. As of 31 December 1995, 1024 patients had been treated
in either a gene transfer or gene therapy protocol. Much controversy
exists regarding how many of these have benefited from their gene
therapy, and no one has yet been cured.
Public controversy in the field of human gene therapy is driven by
several factors. Ordinary citizens as well as scientists easily
understand the enormous potential of gene therapy, but the former may
not appreciate all the pitfalls and uncertainly that lies in the
immediate future. The financial interests of biotechnology firms and,
some have asserted, the career interests of some gene therapists have
encouraged extravagant, or at least overly optimistic, public
statements about contemporary gene therapy. In spite of the
proliferation of protocols, the actual number of patients treated
remains small, and only one genuinely controlled study of human gene
therapy has been published as of this date.
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Wolff J A and Lederberg J. A history of gene transfer and therapy. Chapter 1 in Wolff JA, editor, Gene therapeutics: Methods and applications of direct gene transfer. (Basel: Birkhaeuser) 1994; 3-25.
Report and Recommendations of the Panel to Assess the NIH Investment in
Research on Gene Therapy Available at: