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Int J Biochem Cell Biol. 2014 Jun;51:10-8. doi: 10.1016/j.biocel.2014.03.008. Epub 2014 Mar 22.

Blocking interaction of viral gp120 and CD4-expressing T cells by single-stranded DNA aptamers.

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  • 1Department of Pathology and Genomic Medicine, Houston Methodist Hospital, and Cancer Pathology Laboratory, Houston Methodist Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
  • 2Department 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: yzu@houstonmethodist.org.

Abstract

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.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

HIV infection prevention; Hybrid SELEX; Specific blocking; gp120; ssDNA CD4 aptamer

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