No abstract

Among various gene therapy methods for cancer, suicide gene therapy attracts a special attention because it allows selective conversion of non-toxic compounds into cytotoxic drugs inside cancer cells. As a result, therapeutic index can be increased significantly by introducing high concentrations of cytotoxic molecules to the tumor environment while minimizing impact on normal tissues. Despite significant success at the preclinical level, no cancer suicide gene therapy protocol has delivered the desirable clinical significance yet. This review gives a critical look at the six main enzyme/prodrug systems that are used in suicide gene therapy of cancer and familiarizes readers with the state-of-the-art research and practices in this field. For each enzyme/prodrug system, the mechanisms of action, protein engineering strategies to enhance enzyme stability/affinity and chemical modification techniques to increase prodrug kinetics and potency are discussed. In each category, major clinical trials that have been performed in the past decade with each enzyme/prodrug system are discussed to highlight the progress to date. Finally, shortcomings are underlined and areas that need improvement in order to produce clinical significance are delineated.

No abstract

These results suggest the potential of SELPs in local adenoviral delivery to solid tumors as an alternative approach to intratumoral virus infusion.

Designer biomimetic vectors are genetically engineered biomacromolecules that are designed to mimic viral characteristics in order to overcome the cellular barriers associated with the targeted gene transfer. The vector in this study was genetically engineered to contain at precise locations: a) four tandem repeating units of N-terminal domain of histone H2A to condense DNA into stable nanosize particles suitable for cellular uptake, b) a model targeting motif to target HER2 and enhance internalization of nanoparticles, and c) a pH-responsive synthetic fusogenic peptide to disrupt endosome membranes and promote escape of the nanoparticles into the cytosol. The results demonstrate that a fully functional, multi-domain, designer vector can be engineered to target cells with high specificity, overcome the biological barriers associated with targeted gene transfer, and mediate efficient gene transfer.