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PURPOSE OF THE STUDY. Since the discovery of RNA interference within mammalian cells in 2001, RNA interference has become a significant bench research tool and presents a new therapeutic modality against viral infections and cancer. The purpose of this study was to determine whether a novel method for delivery of small interfering RNAs (siRNAs) to T cells can suppress HIV viral infection.
STUDY POPULATION. A humanized mouse model of AIDS was used to demonstrate in vivo effects.
METHODS. A CD7-specific antibody conjugated to a peptide was used to deliver siRNA to target cells in mice reconstituted with human lymphocytes or CD34+ stem cells. Anti–chemokine receptor 5 (viral coreceptor) complexed with antiviral siRNAs was also used in HIV-infected mice.
RESULTS. Treatment controlled viral replication, prevented disease-associated CD4+ T cell loss, suppressed endogenous virus, and restored CD4+ T cell counts. In addition, it was demonstrated that antiviral siRNAs could be delivered to naive T cells and effectively suppress viremia.
CONCLUSIONS. siRNA therapy for HIV infection seems to be feasible in a preclinical animal model.
REVIEWER COMMENTS. The annual rate of new HIV infections around the globe was 2.7 million in 2007, with 14% of these cases (370 000 cases) occurring in children <15 years of age (1013 cases per day). RNA interference holds considerable potential for antiviral therapy, but delivering effective quantities of siRNAs into the right target cells in vivo represents a considerable challenge. Several small clinical trials using siRNAs are currently underway. This study represents a significant advance for 2 reasons: (1) the findings heighten the prospect of a new HIV-1/AIDS therapy and (2) this study provides a siRNA delivery system that might be adapted to target various receptors and thus other cell types.
- Copyright © 2009 by the American Academy of Pediatrics