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One strategy for gene therapy in malignant disease is gene directed enzyme prodrug therapy (GDEPT). An exogenous enzyme gene is delivered to tumour cells. The enzyme, when expressed, can convert a non-toxic prodrug into a cytotoxic species that is capable of killing the cell in which it has been produced. The most frequently used systems are HSV thymidine kinase with ganciclovir and E. coli cytosine deaminase with 5-fluorocytosine, The bystander effect is of key importance to GDEPT: This describes the local spread of active species from cells that express the enzyme to kill adjacent, untransduced cells. The ultimate success of GDEPT will depend on the ability to achieve efficient gene delivery to and expression in target cells, whilst minimising expression in other tissues. A variety of techniques exist to achieve this goal, including loco-regional administration, manipulation of tumour blood supply and use of tumour-specific promoters to drive enzyme gene expression.

Original publication

DOI

10.1016/S0169-409X(97)00033-1

Type

Journal article

Journal

Advanced Drug Delivery Reviews

Publication Date

07/07/1997

Volume

26

Pages

173 - 184