[Downregulation of human CCR5 receptor gene expression using artificial microRNAs]

Chemokine receptor CCR5 is essential for human immunodeficiency virus (HIV) entry into the sensitive cells. The CCR5 inactivation is believed to be one of the promising approaches in HIV therapy, including gene therapy. A powerful mechanism that enables to regulate gene expression is RNA interference which could be exploited to knockdown CCR5 gene. Here, three artificial microRNAs directed against the human CCR5 receptor gene were generated and their silencing activity in indicator cells developed on the basis of the HT1080 cell line was evaluated. Multiplexing of two or more artificial microRNAs in one transcript has been demonstrated to enhance the gene silencing. A 95% reduction of the CCR5 expression has been achieved using the most efficient microRNA combination.