Résumé :
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Convincing evidence continues to emerge from clinical trials that gene therapy is yielding therapeutic effects in patients suffering from a wide range of diseases. Despite these successes, there have been concerns regarding the efficacy and safety of some gene delivery approaches. The major limiting factors are insufficient and/or transient transgene expression levels and inappropriate expression of the transgene in unwanted cell types. The robustness and safety of gene therapy can be substantially improved by enhancing targeted tissue-specific expression of the therapeutic transgene using synthetic biology. To improve transcriptional targeting for tissue-directed gene therapy, we used a genome-wide bioinformatics approach to identify evolutionary conserved cis-acting regulatory modules (CRMs) that contained clusters of transcription factor binding site (TFBS) motifs that determine high tissue-specific gene expression. To achieve this, we used a novel computational design based on a modified distance difference matrix (DDM)–multidimensional scaling (MDS) approach...
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