Recent developments and current status of gene therapy using viral vectors in the United Kingdom

Introduction

Viral vectors remain the vehicles of choice for gene transfer in clinical trials of gene therapy in the United Kingdom and worldwide. In the United Kingdom alone, 88 clinical trials are registered with the Gene Therapy Advisory Committee (GTAC, www.advisorybodies.doh.gov.uk/genetics/gtac).

Although notable successes have been achieved in some inherited diseases, viral vectors have not been without their problems. We review the adverse events encountered to date and describe lessons that can be learnt from them to improve vector biology and pharmacology in order to make gene therapy with viral vectors a viable treatment for the future.

Sources and selection criteria

We searched Medline and Google, using the terms “gene therapy” and “viral vectors.” We also studied the websites www.wiley.co.uk/genmed/clinical and www.advisorybodies.doh.gov.uk/genetics/gtac for information on ongoing trials using viral vectors in the United Kingdom.

Viral gene therapy: successes and failures

In April 2002 the BBC online news service in the United Kingdom carried an emotive headline: “Bubble boy saved by gene therapy.”1 The 18 month old infant featured had a rare immune disorder, X linked severe combined immunodeficiency (X-SCID), caused by a defective gene on the X chromosome. This gene encodes the common γC chain, an essential component of five cytokine receptors, all of which are necessary for the development of T cells and natural killer cells. Without the γC chain, mature T cells and natural killer cells are completely absent, whereas B cells are usually present in normal or increased numbers. X-SCID is fatal during the first year of life because of severe recurrent infections. As a result, much of the child's short life is spent in a sterile plastic bubble, a barrier to potentially life threatening infectious organisms. A collaboration of scientists from London, Paris, and Milan used a retroviral vector to introduce a functional copy of the defective gene into bone marrow stem cells taken from …