Journal of Molecular Medicine

, Volume 74, Issue 7, pp 379–392

Cell type specific and inducible promoters for vectors in gene therapy as an approach for cell targeting

  • W. Walther
  • U. Stein
Review

DOI: 10.1007/BF00210632

Cite this article as:
Walther, W. & Stein, U. J Mol Med (1996) 74: 379. doi:10.1007/BF00210632

Abstract

Gene therapy is used to correct genetic defects or to deliver new therapeutic functions to the target cells. Viral vectors are employed mainly as a gene delivery system. A great variety of viral expression systems have been developed and assessed for their ability to transfer genes into somatic cells. In particular, retroviral and adenoviral mediated gene transfer have been extensively studied and improved. Preclinical and clinical studies covering a large range of genetic disorders are currently underway to solve basic issues dealing with gene transfer efficiencies, regulation of gene expression, and potential risks of the use of viral vectors. The majority of clinical gene therapy trials that employ viral vectors perform ex vivo gene transfer into target cells. The main issue in potential clinical application of gene therapy is the need for increased gene transfer efficiency and target specificity associated with regulated gene expression at therapeutically relevant levels in vivo. Gene regulatory elements, such as promoters and enhancers, possess cell type specific activities and can be activated by certain induction factors (e.g., hormones, growth factors, cytokines, cytostatics, irradiation, heat shock) via responsive elements. A controlled and restricted expression of these genes can be achieved using such regulatory elements as internal promoters to drive the expression of therapeutic genes in viral vector constructs. In addition to high level and efficient gene expression, minimizing or excluding inappropriate gene expression in surrounding nontarget cells is of great importance for numerous gene therapeutic approaches. This contribution furnishes insight into the field of cell type specific promoter and enhancer systems which have been used for targeted and inducible expression of therapeutic genes in certain genetic disorders, viral infections, and malignancies. We also discuss promoters that represent attractive candidates for the construction of viral vectors.

Key words

Gene therapyTargetingViral expression vectorsPromoterCell type specific

Abbreviations

ADA

Adenosine deaminase

AFP

α-Fetoprotein

AIDS

Acquired immunodeficiency syndrome

CAT

Chloramphenicol acetyltransferase

CD

Cytosine deaminase

CEA

Carcinoembryonic antigen

DMD

Duchenne muscular dystrophy

5-FC

5-Fluorocytosine

HIV

Human immunodeficiency virus

LAD

Leukocyte adherence deficiency

LCR

Locus control region

LTR

Long terminal repeats

MCK

Muscle creatinine kinase

MLV

Moloney murine leukemia virus

MMTV

Mouse mammary tumor virus

PEPCK

Phosphoenolpyruvate carboxykinase

PSA

Prostate-specific antigen

SCLC

Small cell lung cancer cells

SLPI

Secretory leukoprotease inhibitor

SPA/B/C

Human surfactant protein A/B/C

TAR

Trans-activation-responsive

TNF

Tumor necrosis factor-α

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • W. Walther
    • 1
  • U. Stein
    • 1
  1. 1.Max Delbrück Center for Molecular MedicineBerlinGermany