Current gene therapy
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Current gene therapy · Jan 2015
CFTR inactivation by lentiviral vector-mediated RNA interference and CRISPR-Cas9 genome editing in human airway epithelial cells.
Polarized airway epithelial cell cultures modelling Cystic Fibrosis Transmembrane conductance Regulator (CFTR) defect are crucial for CF and biomedical research. RNA interference has proven its value to generate knockdown models for various pathologies. More recently, genome editing using CRISPR-Cas9 artificial endonuclease was a valuable addition to the toolbox of gene inactivation. ⋯ We generated CFTR inactivated cell lines and demonstrated that CRISPR-Cas9 vectorised in a single LVV efficiently promotes CFTR inactivation in primary HAECs. These results provide a new protocol to engineer CF primary epithelia with their isogenic controls and pave the way for manipulation of CFTR expression in these cultures.
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Current gene therapy · Feb 2014
ReviewGenetically redirected T lymphocytes for adoptive immunotherapy of solid tumors.
Genetic engineering of T lymphocytes to confer new antitumor specificities is a fascinating approach that may help the successful clinical translation of adoptive immunotherapy strategies. The recognition of tumor-specific antigens may be obtained inducing the membrane expression of transgene encoded antitumor T cell receptors (TCR) or chimeric antigen receptors (CAR). ⋯ In this work, we will focus on TCR and CAR redirected T lymphocytes as adoptive immunotherapy for solid tumors. We will review the main topics of these strategies from the angle of clinical applications, discussing the main issues that emerged from early clinical trials and their impact on next study designs.
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Current gene therapy · Feb 2013
ReviewStrategies to improve the clinical performance of chimeric antigen receptor-modified T cells for cancer.
Clinical trials of chimeric antigen receptor (CAR)-modified T cells have shown promise in hematologic malignancies. However, in solid tumors, the clinical responses have been less impressive. ⋯ In this review, we focus on recent clinical trials and analyze the factors that determine clinical responses, including the following: 1) the composition of the CAR; 2) the preparation of CAR-modified T Cells; 3) the clinical treatment schedule; 4) the patient characteristics. We also propose future Strategies that must be investigated before the technology can be used in a wider range of clinical applications.
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Current gene therapy · May 2002
ReviewRestoration of transgene expression in hematopoietic cells with drug-selectable marker genes.
Somatic gene therapy is supposed to cure life-threatening hematopoietic disorders but is limited by unstable transgene expression. Efficient gene transfer to hematopoietic progenitor cells does not ensure long-term gene expression. It would therefore be advantageous if the expression of transgenes could be restored in bone marrow. ⋯ Bicistronic vectors have been constructed for coexpression of drug resistance genes and non-selectable, therapeutic genes with the use of an internal ribosomal entry-site (IRES). With the use of bicistronic vectors, expression and function of therapeutic genes have been increased in tissue culture and in animal models. Further preclinical investigations are needed to identify optimal conditions for selection.