Inhibition of HIV-1 protease expression in T cells owing to DNA aptamer-mediated specific delivery of siRNA

Eur J Med Chem. 2012 Oct:56:396-9. doi: 10.1016/j.ejmech.2012.07.045. Epub 2012 Aug 3.

Abstract

Targeted delivery is a promising way to improve the safety and efficiency of siRNA delivery. We show that a DNA aptamer could be used to deliver siRNA into CD4(+) T cells specifically. The DNA aptamer was obtained from the conversion of a reported RNA aptamer that binds to CD4 protein on the surface of T cells. It was covalently conjugated to the sense strand of the siRNA targeting HIV-1 protease (HIV-PR). The resulting DNA aptamer-siRNA chimera could specifically enter into CD4(+) T cells and efficiently knock down the expression of exogenous HIV-PR gene. This study provides the first evidence that the DNA aptamer with intrinsic stability has a greater potential to be used for siRNA delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / metabolism*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Drug Delivery Systems*
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Enzymologic / genetics
  • HIV Protease / genetics
  • HIV Protease / metabolism*
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / pharmacology*

Substances

  • Aptamers, Nucleotide
  • Protease Inhibitors
  • RNA, Small Interfering
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1