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Gene therapy I: principles and clinical applications

Part 1. Genetics

1.7. Gene Therapy

Introductory Review

  1. J. Wesley Ulm

Published Online: 15 JUL 2005

DOI: 10.1002/047001153X.g107115

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

How to Cite

Ulm, J. W. 2005. Gene therapy I: principles and clinical applications. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. 1:1.7:90.

Author Information

  1. Harvard Medical School, Brookline, MA, USA

Publication History

  1. Published Online: 15 JUL 2005

Abstract

Gene therapy encompasses a recently developed group of pharmaceuticals in which the therapeutic agent consists of nucleic acid sequences – DNA, RNA, or some modification thereof – rather than a small molecule. The field arose in the 1980s in the wake of improvements in recombinant DNA technology, and in the midst of better comprehension of gene regulation and modulation processes that could be exploited to construct practical gene therapy systems. Most gene therapy vectors are viral in nature, with retroviruses, adenoviruses, and AAVs (adeno-associated viruses) dominating most protocols, and they have been applied to treat a wide variety of disease subtypes: inherited genetic disorders, cancer, protein aggregation diseases, cardiovascular diseases, and infectious diseases have all been considered in proposed modalities. Gene therapy offers the potential to treat disease with an unprecedented selectivity and therapeutic index, and to allow the flexible design of new pharmaceutical agents on a much more rapid scale than in most traditional schemes. However, technical obstacles related to vector delivery, adequate expression levels, and persistence of viral transgenic sequences continue to pose difficult challenges for clinical application. This article reviews the basic gene therapy principles, common vectors and disease targets, and clinical approaches to convey the current state of the field and its future directions.

Keywords:

  • gene therapy;
  • gene replacement;
  • cystic fibrosis;
  • sickle-cell anemia;
  • cancer;
  • neoplastic disease;
  • cancer vaccines;
  • retrovirus;
  • adenovirus;
  • oncolytic viruses;
  • angiogenesis;
  • adeno-associated virus (AAV);
  • herpesvirus;
  • amplicon;
  • Epstein–Barr virus (EBV);
  • antisense RNA;
  • RNAi;
  • siRNA;
  • gene correction;
  • chimeraplasty;
  • clinical trials