Introduction

What is gene therapy?

Gene therapy has traditionally been defined as the delivery of exogenous genetic material to a cell - most commonly to replace defective genes causing monogenetic disorders. This allows cells to produce proteins that are otherwise absent or not transcribed in sufficient quantities. Since its inception over 40 years ago, the field of gene therapy has expanded tremendously and now includes targeted gene editing strategies in addition to exogenous gene delivery. There are many different approaches to gene therapy as well as a variety of delivery methods and routes of gene transfer. Importantly, gene therapy has the potential to provide long term treatments and cures for previously untreatable or incurable diseases.

What is a vector?

One of the first hurdles that must be overcome for gene therapy to succeed is the efficient introduction of genes into the cell. Vectors are the vehicles that are engineered to do exactly that - deliver genetic material or gene editing machinery to cells. Commonly, vectors are viruses because viruses function by attaching to host cells and transferring their genetic material into the cell as part of their replication cycle. Thus, they can then be used as a gene therapy vehicle to safely deliver a therapeutic gene(s) by removing the viral genes that cause disease and replacing them with the desired genes for transfer [1]. Nonviral delivery methods, on the other hand, introduce naked or plasmid DNA into cells using a variety of techniques such as electroporation [2], nanoparticle delivery [3] and direct injection [4][5]. Both viral and nonviral delivery methods have their respective advantages and disadvantages which are explained in more detail in the Basic Science module. Finally, hybrid techniques, which combine both viral and nonviral methods, are also possible [6].

What are the routes of gene transfer?

Exogenous DNA and/or gene editing machinery can be introduced into cells directly in vivo or a patient’s cells can be temporarily removed from the body, treated ex vivo and subsequently transplanted back again. Clinical application of ex vivo gene therapy has largely been used to treat hematologic and immunologic disorders by targeting hematopoietic stem cells [7][8] although other monogenic disorders and cancers have also been pursued. In vivo gene transfer has been demonstrated extensively in animal models and has more recently been explored in human clinical trials [9].