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Development of Cell-type specific anti-HIV gp120 aptamers for siRNA delivery
Published on: June 23, 2011
Transmembrane protein aptamers that inhibit CCR5 expression and HIV coreceptor function.
Elizabeth H Scheideman1, Sara A Marlatt, Yanhua Xie
1Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.
Journal of Virology
|July 20, 2012
Summary
Scientists engineered novel small proteins, called traptamers, that target the CCR5 coreceptor to block HIV-1 infection. These traptamers show significant potential for developing new HIV prevention strategies.
Area of Science:
- Biochemistry
- Virology
- Drug Discovery
Background:
- HIV-1 entry into human T cells relies on the CCR5 coreceptor.
- Targeting CCR5 is a validated strategy for inhibiting HIV-1 infection.
Purpose of the Study:
- To engineer novel small proteins that inhibit HIV-1 infection by targeting CCR5.
- To investigate the mechanism of action and efficacy of these engineered proteins.
Main Methods:
- Screening a library of artificial transmembrane proteins (traptamers) with randomized domains.
- Assessing traptamer inhibition of HIV-1 reporter virus transduction in human T cells.
- Evaluating traptamer effects on CCR5 expression and HIV-1 replication.
Main Results:
- Six traptamers were identified that inhibit cell surface and total CCR5 expression.
- Optimized traptamers achieved >95% inhibition of R5-tropic HIV-1 reporter virus transduction.
- Traptamers inhibited HIV-1 replication, including against a maraviroc-resistant strain, without affecting CD4 or CXCR4.
Conclusions:
- Engineered traptamers effectively inhibit HIV-1 infection by interfering with CCR5.
- These novel proteins offer a new therapeutic avenue for HIV prevention and treatment.
- Traptamers can serve as tools to study CCR5 structure and function.
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