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Current Gene Therapy

Volume 9 Issue 6
ISSN: 1566-5232
eISSN: 1875-5631

 

   All Titles

  State-of-the-Art Lentiviral Vectors for Research Use: Risk Assessment and Biosafety Recommendations
  pp.459-474 (16) Authors: Katia Pauwels, Rik Gijsbers, Jaan Toelen, Axel Schambach, Karen Willard-Gallo, Celine Verheust, Zeger Debyser, Philippe Herman
 
 
      Abstract

Lentiviral vectors (LV) are competent gene transfer vehicles, as used for both research and gene therapy applications, because of their stable integration in non-dividing and dividing cells and long-term transgene expression. Along with our understanding that LV offer solutions for gene therapy, biosafety concerns have uncovered risks due to insertional mutagenesis, the generation of replication competent lentiviruses (RCL) and vector mobilization. Researchers therefore continue to devote significant efforts in designing LV with improved efficacy and biosafety features.

The choice of a particular LV system for experimental studies is often driven by functional considerations, including increased productivity and/or transduction efficiency. The design of safer vectors has also directly benefited researchers allowing them to conduct experimental studies with lower risk. Currently, vectors combine improved safety features (that decrease the risk of recombination and vector mobilization) with increased transduction efficiency. Hence, risks associated with the inadvertent transduction of cells of the investigator gain greater importance in assessing the overall risk of these vectors and become an important biosafety concern.

This review outlines the different strategies used to improve LV biosafety by comparing state-of-the-art and emerging LV production systems and highlighting biosafety issues that can arise during their contained use. The few existing national and international biosafety recommendations that specifically address the use of LV in research are discussed and recommendations for most common research activities using LV are proposed.

 
  Keywords: Lentivirus, vector production, biosafety, vector design, guidelines, HIV-1 derived vector, gene transfer, splitpackaging
  Affiliation: Scientific Institute of Public Health, Division of Biosafety and Biotechnology, J. Wytsmanstraat 14, B- 1050 Brussels, Belgium.
 
  Key: New Content Free Content Open Access Plus Subscribed Content

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