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Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy.

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.

journal_name

Mol Ther Methods Clin Dev

journal_title

Molecular therapy. Methods & clinical development

authors

Biasco L,Rothe M,Büning H,Schambach A

doi

10.1016/j.omtm.2017.10.002

subject

Has Abstract

pub_date

2017-10-05 00:00:00

pages

21-30

issn

2329-0501

pii

S2329-0501(17)30109-2

journal_volume

8

pub_type

杂志文章,评审

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