Downregulation of human CCR5 gene expression with artificial microRNAs

Abstract

Chemokine receptor 5 (CCR5) is one of the two coreceptors that are utilized by the human immunodeficiency virus (HIV) to enter the cell. CCR5 inactivation is considered to be a promising approach to HIV therapy, including gene therapy. RNA interference provides a powerful tool to regulate gene expression and may be utilized to knockdown the CCR5 gene. Three artificial microRNAs (amiRNAs) directed to the human CCR5 gene were constructed, and their silencing activity was tested in indicator cells, which were derived from the HT1080 human cell line. A multiplexing of two or more amiRNAs in one transcript was shown to enhance the CCR5 gene silencing. A 95% reduction of CCR5 expression was achieved with the most efficient amiRNA combination.