GENE-TRANSFER BY VIRAL VECTORS FOR GENE-THERAPY

In a review article Miller [1] reported on the state of the art of hum an gene therapy as it was summarized in a meeting at the end of Decemb er 1991. The human trials in which human genes were successfully trans ferred in vitro to mark cells of patients and for gene therapy of gene tic disorders. The approved gene therapy trials are based on the use o f: (a) retroviral vectors and (b) liposomes which contain plasmid DNA that have been found useful in gene transfer into human cells under cu lture conditions in vitro for administration to the donor of the cell by injection. One of the aims of human gene therapy is to advance anti cancer treatment protocols by using human genes whose products have be en shown to have suppressive effects on tumor progression. Another aim is to introduce an active human gene which is missing in patients wit h single gene mutations (e.g., low-density lipoprotein receptor gene t ransfer to hepatocytes from low-density lipoprotein receptor deficient patients; adenosine desaminase gene transfer to lymphocytes from aden osine desaminase deficient patients [1]). The crucial elements in gene therapy are the gene delivery vectors. The approved gene transfer tri als in human cells utilize retroviral vectors from which all the viral genes are removed or altered and replication of viral genes is suppor ted by cells engineered to provide to the modified retroviral genomes which the viral proteins need for virion budding and for the productio n of mature virions. This technique has advantages and disadvantages. In the forthcoming volume Gene Transfer by Viral Vectors for Gene Ther apy [2] we plan to provide a forum for the analysis of developments in the construction and use of viral vectors useful for gene therapy [3- 7].