Safety of retroviral vectors in clinical applications: lessons from retroviral biology and pathogenesis

Neil, J. C. (2017) Safety of retroviral vectors in clinical applications: lessons from retroviral biology and pathogenesis. In: eLS: Essentials for Life Science. Wiley. (doi:10.1002/9780470015902.a0024847)

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Abstract

The ability of retroviruses to integrate a precise copy of the viral genome into host cell DNA (deoxyribonucleic acid) has been harnessed in the development of retroviral vectors for stable delivery of foreign genes to target cells. Over several decades, these tools have been utilised in human medicine in diverse applications from cell lineage tracing by gene marking to correction of single-gene disorders and therapy of cancer. The unanticipated occurrence of leukaemias due to vector insertional mutagenesis in trials of gene therapy led to an urgent search for safer vectors and delivery systems. The advent of T-cell therapy for cancer has led to renewed interest in retroviral vectors as stable and efficient delivery vehicles and is supported by observations suggesting that mature T cells are relatively resistant to oncogenic transformation by retroviruses. However, this evidence is circumstantial and the long-term risks are poorly understood. Retroviral vector safety is considered here from the perspective of the biology and pathogenesis of their parental viruses. It is suggested that robust cell suicide strategies to remove transduced cells are likely to be important if retroviral vectors are to be adopted widely for delivery of T-cell therapy for cancer and other diseases.

Item Type:Book Sections (Encyclopaedia entry)
Status:Published
Glasgow Author(s) Enlighten ID:Neil, Professor James
Authors: Neil, J. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Publisher:Wiley

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
539393New Approaches to Modelling Human LeukaemiaEwan CameronBloodwise (BLOODWIS)13046VET - PATHOLOGY, PUBLIC H & DISEASE INV