Current development of nonviral-mediated gene transfer

Abstract

Nonviral-mediated gene transfer was used in human gene therapy clinical trials that dealt with the treatment of inherited or acquired genetic disorders and cancer. Several preclinical studies are currently ongoing to employ nonviral vectors in genetic immunization programs for a variety of infectious diseases. The interest in nonviral-mediated gene transfer is motivated by two main reasons: (I) nonviral-based vectors do not derive from infectious agents and are minimally toxic; and (II) they can be easily produced in large quantities. However, the main drawbacks of nonviral-mediated gene transfer are related to low transfection efficiency of target cells, especially in vivo, and to the transient nature of transgene expression. These drawbacks render nonviral-mediated gene transfer not particularly suitable for the treatment of pathological conditions that require long-term transgene expression, such as neurodegenerative disorders and inherited or acquired genetic diseases. On these grounds, the optimal application of nonviral-mediated gene transfer is in immunotherapy for cancer and infectious diseases, as a transient expression of the transgene might be sufficient to trigger effective and durable host immune responses. The purpose of this review is to summarize the standpoint of nonviral vector development.