Conclusions And Future Prospects

We have argued in this review that drug-selectable marker genes may be helpful for gene therapy in two ways: first, to protect bone marrow progenitor cells (and other sensitive cells) from the cytotoxicity of anticancer drugs, thereby allowing safe chemotherapeutic treatment at reduced risk of severe side effects, and second, to enrich the expression of otherwise nonselectable genes in drug-sensitive cells to overcome low or unstable gene expression in vivo. Given the current instability of expression of genes from existing vectors, especially episomal vectors, such selectable markers may be an essential component of gene therapy protocols.

We are still in the early stages of vector development, and until transduction efficiencies into human tissues such as bone marrow are improved and shown to be safe, long-term human gene therapy will not be feasible. The combination of more efficient gene transfer targeted vector systems, and effective, relatively nontoxic selection systems to maintain gene expression may make long-term correction of human genetic defects feasible and safe.

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