Biasco, L;
Rothe, M;
Büning, H;
Schambach, A;
(2018)
Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy.
Molecular Therapy: Methods & Clinical Development
, 8
pp. 21-30.
10.1016/j.omtm.2017.10.002.
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Abstract
Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes. Although improvements in vector design clearly lowered the risk of this insertional mutagenesis, analysis of potential genotoxicity and the consequences of vector integration remain important parameters for basic and translational research and most importantly for the clinic. Here, we review current assays to analyze biodistribution and genotoxicity in the pre-clinical setting and describe tools to monitor vector integration sites in vector-treated patients as a biosafety readout.
| Type: | Article |
|---|---|
| Title: | Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.omtm.2017.10.002 |
| Publisher version: | https://doi.org/10.1016/j.omtm.2017.10.002 |
| Language: | English |
| Additional information: | Copyright © 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | AAV, clinical translation, gammaretroviral, gene therapy, insertional mutagenesis, lentiviral, regulatory authorities, vector |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10048987 |
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