Title:Biosafety Challenges for Use of Lentiviral Vectors in Gene Therapy
VOLUME: 13 ISSUE: 6
Author(s):Michael Rothe, Ute Modlich and Axel Schambach
Affiliation:Institute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-StraBe 1 D-30625 Hannover, Germany.
Keywords:Clinical trials, gene therapy, lentiviral vector, monitoring, risk factors.
Abstract:Lentiviral vectors are promising tools for the genetic modification of cells in biomedical research and gene
therapy. Their use in recent clinical trials for the treatment of adrenoleukodystrophy, β-thalassemia, Wiskott-Aldrich-
Syndrome and metachromatic leukodystrophy underlined their efficacy for therapies especially in case of hereditary diseases.
In comparison to gammaretroviral LTR-driven vectors, which were employed in the first clinical trials, lentiviral
vectors present with some favorable features like the ability to transduce also non-dividing cells and a potentially safer insertion
profile. However, genetic modification with viral vectors in general and stable integration of the therapeutic gene
into the host cell genome bear concerns with respect to different levels of personal or environmental safety. Among them,
insertional mutagenesis by enhancer mediated dysregulation of neighboring genes or aberrant splicing is still the biggest
concern. However, also risks like immunogenicity of vector particles, the phenotoxicity of the transgene and potential vertical
or horizontal transmission by replication competent retroviruses need to be taken into account. This review will give
an overview on biosafety aspects that are relevant to the use of lentiviral vectors for genetic modification and gene therapy.
Furthermore, assay systems aiming at evaluating biosafety in preclinical settings and recent promising clinical trials
including efforts of monitoring of patients after gene therapy will be discussed.
