Blocking interaction of viral gp120 and CD4-expressing T cells by single-stranded DNA aptamers
- Int J Biochem Cell Biol. 2014 Jun:51:10-8. doi: 10.1016/j.biocel.2014.03.008.
- 1. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, and Cancer Pathology Laboratory, Houston Methodist Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
- 2. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, and Cancer Pathology Laboratory, Houston Methodist Research Institute, 6565 Fannin Street, Houston, TX 77030, USA. Electronic address: [email protected].
To investigate the potential clinical application of Aptamers to prevention of HIV Infection, single-stranded DNA (ssDNA) Aptamers specific for CD4 were developed using the systematic evolution of ligands by exponential enrichment approach and next generation Sequencing. In contrast to RNA-based Aptamers, the developed ssDNA Aptamers were stable in human serum up to 12h. Cell binding assays revealed that the Aptamers specifically targeted CD4-expressing cells with high binding affinity (Kd=1.59nM), a concentration within the range required for therapeutic application. Importantly, the Aptamers selectively bound CD4 on human cells and disrupted the interaction of viral gp120 to CD4 receptors, which is a prerequisite step of HIV-1 Infection. Functional studies showed that the aptamer Polymers significantly blocked binding of viral gp120 to CD4-expressing cells by up to 70% inhibition. These findings provide a new approach to prevent HIV-1 transmission using oligonucleotide Aptamers.
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