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A side-effect free chemotherapy for treating cancer by directed gene delivery and a prodrug

A. C. Matin

Chemotherapy with no or minimal side effects is an urgent need. One means of attaining it is through gene-delivered prodrug therapies (GDEPTs). Prodrugs are harmless until activated by a bacterial or viral gene product; they can kill tumors without side effects if the activating gene is specifically delivered to cancer. Previous GDEPT approaches have been hampered from low gene delivery and duration of expression; insufficient bystander effect; use of viruses as gene delivery vehicles; and the need to inject the gene directly into the tumor – the latter minimizes GDEPT applicability, since many cancers, particularly cancer metastases, are not amenable to direct gene injection. My collaborators and I have addressed these problems. The use of the prodrug CNOB (C16H7CIN2O4) that we discovered facilitated this because its activated drug MCHB (C16H9CIN2O2) can be quantitatively visualized in living mice; and by using exosomes (EVs) for gene delivery.