AI Article Synopsis
- Retroviral and lentiviral vectors can pose a risk of insertional mutagenesis, potentially leading to health issues like cancer in mouse models and certain patients with severe genetic disorders.
- A significant challenge in using these vectors for gene therapy is ensuring stable gene expression while minimizing these risks.
- New studies have demonstrated that integration-deficient lentiviral vectors can effectively deliver genes in living rodents, providing long-lasting gene expression and offering potential treatments for conditions like retinal degeneration without integrating into the host's chromosomes.
Article Abstract
Retroviral and lentiviral vector integration into host-cell chromosomes carries with it a finite chance of causing insertional mutagenesis. This risk has been highlighted by the induction of malignancy in mouse models, and development of lymphoproliferative disease in three individuals with severe combined immunodeficiency-X1 (refs. 2,3). Therefore, a key challenge for clinical therapies based on retroviral vectors is to achieve stable transgene expression while minimizing insertional mutagenesis. Recent in vitro studies have shown that integration-deficient lentiviral vectors can mediate stable transduction. With similar vectors, we now show efficient and sustained transgene expression in vivo in rodent ocular and brain tissues. We also show substantial rescue of clinically relevant rodent models of retinal degeneration. Therefore, the high efficiency of gene transfer and expression mediated by lentiviruses can be harnessed in vivo without a requirement for vector integration. For therapeutic application to postmitotic tissues, this system substantially reduces the risk of insertional mutagenesis.
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