Lentiviral vectors (LVs) are a highly valuable tool for gene transfer currently exploited in basic, applied, and clinical studies. The authors of this study have previously reported successful, transient and stable production of LVs pseudotyped with RD114-TR for good transduction of T lymphocytes and CD34+ cells. In this work, to simplify the vector design, they decided to codon-optimize the entire RD114-TR ORF. In fact, the elimination of the interfering sequences would have avoided using the BGI, therefore reducing the size of the vector. Unexpectedly, they found that, despite the high level of transcription/translation and cytosol export, RD114-TRco is functionally dead. These data strengthen the conclusion, also supported by other studies, that codon optimization may not always lead to functional improvement of the gene of interest.
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Lentiviral vectors (LVs) are a highly valuable tool for gene transfer currently exploited in basic, applied, and clinical studies. The authors of this study have previously reported successful, transient and stable production of LVs pseudotyped with RD114-TR for good transduction of T lymphocytes and CD34+ cells. In this work, to simplify the vector design, they decided to codon-optimize the entire RD114-TR ORF. In fact, the elimination of the interfering sequences would have avoided using the BGI, therefore reducing the size of the vector. Unexpectedly, they found that, despite the high level of transcription/translation and cytosol export, RD114-TRco is functionally dead. These data strengthen the conclusion, also supported by other studies, that codon optimization may not always lead to functional improvement of the gene of interest.