title: 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.
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, and Cancer Pathology Laboratory, Houston Methodist Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
authors.forename: Nianxi
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, and Cancer Pathology Laboratory, Houston Methodist Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
authors.forename: Sung-nan
authors.initials: SN
authors.lastname: Pei
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, and Cancer Pathology Laboratory, Houston Methodist Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
authors.forename: Parag
authors.initials: P
authors.lastname: Parekh
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, and Cancer Pathology Laboratory, Houston Methodist Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Salazar
authors.affiliation: 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: yzu@houstonmethodist.org.
authors.forename: Youli
authors.initials: Y
authors.lastname: Zu
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000097:blood / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D052156:SELEX Aptamer Technique
chemical_list: D052157:Aptamers, Nucleotide; D004277:DNA, Single-Stranded; D015699:HIV Envelope Protein gp120
keywords: HIV infection prevention; Hybrid SELEX; Specific blocking; gp120; ssDNA CD4 aptamer