Gene therapy is defined as the treatment of disease by transfer of genetic material into cells, to prevent, treat and potentially even cure a disease. Gene therapies can work by several mechanisms: 1) replacing a disease-causing gene with a healthy copy of the gene; 2) inactivating a disease-causing gene that is not functioning properly; 3) introducing a new or modified gene into the body to help treat a disease. There are a variety of types of gene therapy platforms. This presentation will explore the viral vectors available for gene transfer as well as their advantages and disadvantages. Viruses have evolved a natural ability to deliver genetic material into cells and are currently the most commonly used gene therapy platforms. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells. There are three universal requirements for viral gene therapy vectors. First, the delivery system must be safe and immunologically inert. Second, it must protect the genetic material from degradation. Third, the vector must encode an effective therapeutic gene that has sustained expression at a defined target site. Here we will take a deeper look at the advancement achieved over the past 30 years in developing, engineering, and production of highly defective, non-toxic herpes simplex virus (HSV) vectors platforms. We will discuss mechanisms of genetic regulation through cell-specific and inducible promoters, which allow to express gene products only in specific cells and to control their transcriptional activation. We will explore how noncoding DNA regions, such as insulator - small DNA elements that overcome the host’s epigenetic silencing of foreign DNA- are essential in preserving stable transgene expression in vivo. By the end of this presentation the participant would be able to 1) discuss the advantages and disadvantages of gene therapy vector-based platforms; 2) explain HSV-based gene therapy platforms and 3) describe how epigenetic changes play a pivotal role in maintaining transgene expression.

Learning Objectives:

• Discuss the advantages and disadvantages of gene therapy vector based platforms
• Explain HSV-based gene therapy platforms
• Describe how epigenetic changes play a pivotal role in maintaining transgene expression