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


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.

SUBMITTER: Zhao N 

PROVIDER: S-EPMC4041034 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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

Zhao Nianxi N   Pei Sung-nan SN   Parekh Parag P   Salazar Eric E   Zu Youli Y  

The international journal of biochemistry & cell biology 20140322


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=1.59n  ...[more]

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