Recent progress in non-viral gene delivery

Abstract

Gene therapy provides a unique approach to medicine as it can be adapted towards the treatment of both inherited and acquired diseases. Gene delivery relies upon the encapsulation of a gene of interest,which is then ideally delivered to target cells.After uptake up by endocytosis, the DNA must be released into the cell so that transcription and translation may occur to produce the protein of interest.To achieve successful gene delivery, significant barriers must be overcome at each step of this process in order to optimize gene activity while minimizing the potential for inhibitory inflammatory responses. Particular interest has been paid in recent years to the development of efficient nonviral vectors.Viral vectors (i.e., retroviruses and adenoviruses) may provide superior gene delivery to target cells compared to their non-viral counterparts,but viral vectors also come with the significantly increased risk of triggering a specific immune response, which under extreme circumstances could result in death (Lehrman 1999; Marshall 1999). Non-viral vectors may trigger an inflammatory response but are not likely to elicit specific recognition, making these types of vectors less hazardous in terms of antigen-specific immune responses. Although non-viral vectors are more appealing in this respect, there are several other factors that must be considered in vector design, including specific cell targeting, optimized uptake, and efficient intracellular release of the vector, in addition to minimizing the immune response. The development of novel non-viral vectors intended to optimize one or more of these aspects of gene delivery will be discussed briefly in this chapter.