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Lentiviral Vectors in Gene Therapy: Their Current Status and Future Potential

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

The concept of gene therapy originated in the mid twentieth century and was perceived as a revolutionary technology with the promise to cure almost any disease of which the molecular basis was understood. Since then, several gene vectors have been developed and the feasibility of gene therapy has been shown in many animal models of human disease. However, clinical efficacy could not be demonstrated until the beginning of the new century in a small-scale clinical trial curing an otherwise fatal immunodeficiency disorder in children. This first success, achieved after retroviral therapy, was later overshadowed by the occurrence of vector-related leukemia in a significant number of the treated children, demonstrating that the future success of gene therapy depends on our understanding of vector biology. This has led to the development of later-generation vectors with improved efficiency, specificity, and safety. Amongst these are HIV-1 lentivirus-based vectors (lentivectors), which are being increasingly used in basic and applied research. Human gene therapy clinical trials are currently underway using lentivectors in a wide range of human diseases. The intention of this review is to describe the main scientific steps leading to the engineering of HIV-1 lentiviral vectors and place them in the context of current human gene therapy.

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Abbreviations

DC:

Dendritic cell

ds:

Double-stranded

env:

Envelope-encoding gene

gag:

Gene encoding structural proteins

pol:

Gene encoding viral enzymes

HIV:

Human immunodeficiency virus

LTR:

Long terminal repeat

MMP:

Metalloproteinase

MLV:

Murine leukemia virus

NILV:

Non-integrating lentivector

PPT:

Polypurine tract

PSA:

Prostate-specific antigen

SCID:

Severe combined immunodeficiency

ss:

Single-stranded

TCR:

T-cell receptor

VSV G:

Vesicular stomatitis virus glycoprotein

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Acknowledgments

Karine Breckpot is funded by the Fund for Scientific Research-Flanders (FWO-Vlaanderen). David Escors is funded by an Arthritis Research Campaign Career Development Fellowship. We would also like to acknowledge all research groups working in gene therapy that have not been cited in this review.

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Authors and Affiliations

  1. Division of Infection and Immunity, Medical School of the Royal Free and University College London, 46 Cleveland Street, London, W1T 4JF, UK

    David Escors & Karine Breckpot

  2. Laboratory of Molecular and Cellular Therapy, Department of Physiology-Immunology, Medical School of the ‘Vrije Universiteit Brussel’, Laarbeeklaan 103 Building E, 1090, Jette, Belgium

    Karine Breckpot

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  1. David Escors
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  2. Karine Breckpot
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Correspondence to David Escors.

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Escors, D., Breckpot, K. Lentiviral Vectors in Gene Therapy: Their Current Status and Future Potential. Arch. Immunol. Ther. Exp. 58, 107–119 (2010). https://doi.org/10.1007/s00005-010-0063-4

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  • DOI: https://doi.org/10.1007/s00005-010-0063-4

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