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

Review

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.

Keywords

Gene therapy Lentivirus-based vector 

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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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2010

Authors and Affiliations

  1. 1.Division of Infection and ImmunityMedical School of the Royal Free and University College LondonLondonUK
  2. 2.Laboratory of Molecular and Cellular Therapy, Department of Physiology-ImmunologyMedical School of the ‘Vrije Universiteit Brussel’JetteBelgium

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