期刊
GENE THERAPY
卷 9, 期 24, 页码 1730-1734出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3301893
关键词
lentivirus; retrovirus; insertional mutagenesis; oncogenesis; replication competent retrovirus (RCR); human immunodeficiency virus (HIV)
Gene therapy vectors derived from lentiviruses offer many potentially unique advantages over more conventional retroviral gene delivery systems. Principal amongst these is their ability to provide long-term and stable gene expression and to infect non-dividing cells, such as neurons. However the use of lentiviral-based vectors in the clinic also raises specific safety and ethical issues. Concerns include the possible generation of replication competent lentiviruses during vector production, mobilisation of the vector by endogenous retroviruses in the genomes of patients, insertional mutagenesis leading to cancer, germline alteration resulting in transgenerational effects and dissemination of new viruses from gene therapy patients. Investigators proposing to conduct this type of research should take due account of the potential risks for interaction of lentiviral gene therapy vectors with other retroviral elements in human subjects, such as Human Immunodeficiency Virus. In addition, strict quality control for replication competent lentiviruses and suitable measurements of lentiviral infectious particle number will be required before these types of viral vector can proceed to the clinic.
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