Potent suppression of HIV type 1 infection by a short hairpin anti-CXCR4 siRNA

Joseph S Anderson, Akhil Banerjea, Vicente Planelles, Ramesh Akkina

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

The phenomenon of RNA interference (RNAi) sparked a new surge in the area of posttranscriptional gene silencing methodologies and their potential application for HIV-1 gene therapy. A potentially promising strategy is to exploit siRNAs to prevent viral entry at the cell surface by down-regulating essential cell surface HIV-1 coreceptors. In the present studies we targeted the CXCR4 coreceptor for disruption with siRNA to inhibit HIV-1 entry as a first step toward the ultimate goal of translating this to gene therapy for AIDS. A stem-loop hairpin structured anti-CXCR4 siRNA was designed and synthesized in vitro by transcription with T7 polymerase. Down-regulation of the coreceptor was assayed in U373-Magi-CXCR4 cells. FACS analysis showed marked down-regulation of CXCR4 on the cell surface and Western blot analysis confirmed the reduced levels of intracellular synthesis. When challenged with X4-tropic HIV-1 NL4-3, the siRNA-transfected cells exhibited marked viral resistance. Consistent with these results, siRNA-transfected primary lymphocytes also exhibited significant resistance to HIV-1 entry. These proof-of-concept studies demonstrated the efficacy of an siRNA targeted to an essential cellular coreceptor CXCR4 in protecting from HIV-1 infection. Delivery of this siRNA into hematopoietic stem cells via lentiviral vectors may have potential gene therapeutic applications.

Original languageEnglish (US)
Pages (from-to)699-706
Number of pages8
JournalAIDS Research and Human Retroviruses
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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Small Interfering RNA
HIV Infections
HIV-1
RNA Interference
Genetic Therapy
Down-Regulation
Hematopoietic Stem Cells
Acquired Immunodeficiency Syndrome
Western Blotting
Lymphocytes
Genes

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Potent suppression of HIV type 1 infection by a short hairpin anti-CXCR4 siRNA. / Anderson, Joseph S; Banerjea, Akhil; Planelles, Vicente; Akkina, Ramesh.

In: AIDS Research and Human Retroviruses, Vol. 19, No. 8, 01.08.2003, p. 699-706.

Research output: Contribution to journalArticle

Anderson, Joseph S ; Banerjea, Akhil ; Planelles, Vicente ; Akkina, Ramesh. / Potent suppression of HIV type 1 infection by a short hairpin anti-CXCR4 siRNA. In: AIDS Research and Human Retroviruses. 2003 ; Vol. 19, No. 8. pp. 699-706.
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