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Helper-dependent adenoviral vectors for gene therapy
Published on August 5, 2014 57 min
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I want to welcome you to this presentation. My name is Nicola Brunetti-Pierri. And I work as an Associate Investigator at the Telethon Institute of Genetics and Medicine. I'm also affiliated with the Department of Translational Medicine of Federico II University in Naples, Italy. In this talk, I would like to bring your attention to helper-dependent adenoviral vectors and their applications for gene therapy.
Adenoviruses are among the most commonly used vectors in human clinical trials. By 2012, over 420 clinical trials were initiated using adenoviral vectors with the majority being for cancer gene therapy.
Several vectors have been investigated for gene therapy. And so far, no single vector system has yet emerged as clearly superior to the others for all applications. This slide shows an overview of the strengths and weaknesses of adenoviral vectors compared to the most commonly used vectors, including retroviral and lentiviral vectors, AAV vectors and naked plasmid DNA.
Retroviral vectors can only transduce dividing cells, requiring a natural breakdown of the nuclear membrane that occurs during cell division, to enter the nucleus. Therefore, actively dividing cells, such as hematopoietic stem cells are excellent targets for retroviral vector mediated gene therapy, while tissues such as the brain, eye, lung and adult liver are not amenable for in vivo gene delivery. Following the infection of target cells, retroviral genome integrates into the hostage genome, particularly in sites closer to transcriptionally active genes, including proto-oncogenes. Although integration provides the potential for long term transgene expression, because the integrated genome is maintained in the progenial transduced cells, it also increases the risks of cancer formation through insertional mutagenesis or insertional activation of proximal genes as it was observed in the clinical gene therapy trial for X-linked severe combined immunodeficiency.