Episomal Vectors for Gene Therapy

Anja      Ehrhardt; Rudolf      Haase; Aloys      Schepers; Manuel   J.   Deutsch; Hans   J.   Lipps; Armin      Baiker

doi:10.2174/156652308784746440

Abstract

The increasing knowledge of the molecular and genetic background of many different human diseases has led to the vision that genetic engineering might be used one day for their phenotypic correction. The main goal of gene therapy is to treat loss-of-function genetic disorders by delivering correcting therapeutic DNA sequences into the nucleus of a cell, allowing its long-term expression at physiologically relevant levels. Manifold different vector systems for the therapeutic gene delivery have been described over the recent years. They all have their individual advantages but also their individual limitations and must be judged on a careful risk/benefit analysis. Integrating vector systems can deliver genetic material to a target cell with high efficiency enabling long-term expression of an encoded transgene. The main disadvantage of integrating vector systems, however, is their potential risk of causing insertional mutagenesis. Episomal vector systems have the potential to avoid these undesired side effects, since they behave as separate extrachromosomal elements in the nucleus of a target cell. Within this article we present a comprehensive survey of currently available episomal vector systems for the genetic modification of mammalian cells. We will discuss their advantages and disadvantages and their applications in the context of basic research, biotechnology and gene therapy.

Keywords: Gene Therapy, Episomal Vectors, Vector Administration, Vector Replication, Nuclear Retention, Virus-like Particles, Naked DNA delivery, Artificial Chromosomes