Viral vectors: from virology to transgene expression

Abstract

In the late 1970s, it was predicted that gene therapy would be applied to humans within a decade. However, despite some success, gene therapy has still not become a routine practise in medicine. In this review, we will examine the problems, both experimental and clinical, associated with the use of viral material for transgenic insertion. We shall also discuss the development of viral vectors involving the most important vector types derived from retroviruses, adenoviruses, herpes simplex viruses and adeno-associated viruses.

Figure 1

The four main viral vectors: plasmids and viral particles. (a) Recombinant AAV vector. (b) Retroviral vector. (c) Gutless adenoviral vector. (d) Amplicon vector derived from HSV-1. ITR, inverted terminal repeat; L, left; R, right; ψ, a, encapsidation signal; oriS, replication origin.

Figure 2

Overview of gene therapy clinical trials worldwide. (a) Number of trials initiated per year, (b) vectors used and (c) indications addressed. Updated information available from the Journal of Gene Medicine: http://www.wiley.co.uk/genmed/clinical. Reproduced with the permission from Wiley and Son Ltd.

Figure 3

From wild-type virus to replication-defective viral vectors. Outline of the possible modifications of viral properties required to transform a virus into a gene transfer vector.

Figure 4

A few targeting and re-targeting options for viral vectors. Retargeting is necessary to alter the tropism of the viral vectors to reach more efficiently the desired target cells and/or prevent transduction of non-target cells.