Targeting endocytosis and motor proteins to enhance DNA persistence

Gene therapy provides a major new therapeutic strategy for the treatment of disease. Despite its potential for the inhibition of disease progression at the molecular level, gene therapy has faced numerous challenges. Foremost amongst these is the introduction of a sufficient amount of DNA-based drug to the target cell under conditions that encourage persistence of the introduced DNA. Because many DNA-based drugs enter cells via receptor-mediated endocytosis, clearly modulation of this process is a key issue in maximizing DNA persistence. In this review, a particular protein that participates in receptor-mediated endocytosis, the microtubule-based motor protein, cytoplasmic dynein, is introduced. In addition, recent advances in the study of cytoplasmic dynein in receptor-mediated endocytosis are discussed, and there is consideration of the potential of cytoplasmic dynein as a critical target for the regulation of DNA-uptake and persistence.